rs2304371

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002299.4(LCT):c.4606C>T(p.Leu1536Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,613,694 control chromosomes in the GnomAD database, including 536,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 39129 hom., cov: 32)

Exomes 𝑓: 0.82 ( 497659 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.196

Publications

40 publications found

Variant links:

Genes affected

LCT (HGNC:6530): (lactase) The protein encoded by this gene belongs to the glycosyl hydrolase 1 family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme is integral to the plasma membrane and has both phlorizin hydrolase activity and lactase activity. Mutations in this gene are associated with congenital lactase deficiency. Polymorphisms in this gene are associated with lactase persistence, in which intestinal lactase activity persists at childhood levels into adulthood. [provided by RefSeq, Jan 2016]

LCT Gene-Disease associations (from GenCC):

congenital lactase deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

LCT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-135803987-G-A is Benign according to our data. Variant chr2-135803987-G-A is described in ClinVar as Benign. ClinVar VariationId is 331172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.196 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002299.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.4606C>T	p.Leu1536Leu	synonymous	Exon 11 of 17	NP_002290.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.4606C>T	p.Leu1536Leu	synonymous	Exon 11 of 17	ENSP00000264162.2
	LCT	ENST00000452974.1	TSL:1	n.2902C>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000391231.1

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106404

AN:

151974

Hom.:

39124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.658

GnomAD2 exomes

AF:

0.758

AC:

190438

AN:

251288

AF XY:

0.758

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.765

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.819

AC:

1196747

AN:

1461602

Hom.:

497659

Cov.:

AF XY:

0.813

AC XY:

591292

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.458

AC:

15316

AN:

33468

American (AMR)

AF:

0.760

AC:

33991

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

13492

AN:

26132

East Asian (EAS)

AF:

0.808

AC:

32060

AN:

39700

South Asian (SAS)

AF:

0.738

AC:

63601

AN:

86236

European-Finnish (FIN)

AF:

0.837

AC:

44703

AN:

53410

Middle Eastern (MID)

AF:

0.588

AC:

3387

AN:

5758

European-Non Finnish (NFE)

AF:

0.849

AC:

943665

AN:

1111798

Other (OTH)

AF:

0.771

AC:

46532

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12115

24230

36346

48461

60576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21110

42220

63330

84440

105550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.700

AC:

106457

AN:

152092

Hom.:

39129

Cov.:

AF XY:

0.702

AC XY:

52150

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.478

AC:

19818

AN:

41448

American (AMR)

AF:

0.700

AC:

10713

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1796

AN:

3468

East Asian (EAS)

AF:

0.780

AC:

4019

AN:

5154

South Asian (SAS)

AF:

0.746

AC:

3599

AN:

4826

European-Finnish (FIN)

AF:

0.844

AC:

8929

AN:

10584

Middle Eastern (MID)

AF:

0.551

AC:

161

AN:

292

European-Non Finnish (NFE)

AF:

0.813

AC:

55271

AN:

68002

Other (OTH)

AF:

0.654

AC:

1383

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1503

3006

4510

6013

7516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.752

Hom.:

120272

Bravo

AF:

0.682

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Congenital lactase deficiency

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lactose intolerance

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.3

(source)

DANN

Benign

0.68

PhyloP100

0.20

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over