2-135788540-A-G

Variant names:

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.5568T>C(p.Ala1856Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,603,220 control chromosomes in the GnomAD database, including 442,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 29596 hom., cov: 31)

Exomes 𝑓: 0.74 ( 413239 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.140

Publications

26 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=-0.85).

BP6

Variant 2-135788540-A-G is Benign according to our data. Variant chr2-135788540-A-G is described in ClinVar as Benign. ClinVar VariationId is 331164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 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.5568T>C	p.Ala1856Ala	synonymous	Exon 17 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.5568T>C	p.Ala1856Ala	synonymous	Exon 17 of 17	ENSP00000264162.2

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90631

AN:

151862

Hom.:

29593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.537

GnomAD2 exomes

AF:

0.621

AC:

156029

AN:

251154

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.752

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.739

AC:

1072495

AN:

1451240

Hom.:

413239

Cov.:

AF XY:

0.729

AC XY:

526552

AN XY:

722514

show subpopulations

African (AFR)

AF:

0.354

AC:

11786

AN:

33276

American (AMR)

AF:

0.512

AC:

22891

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

11157

AN:

26090

East Asian (EAS)

AF:

0.476

AC:

18862

AN:

39652

South Asian (SAS)

AF:

0.476

AC:

40896

AN:

85982

European-Finnish (FIN)

AF:

0.747

AC:

39865

AN:

53398

Middle Eastern (MID)

AF:

0.362

AC:

1516

AN:

4184

European-Non Finnish (NFE)

AF:

0.802

AC:

885061

AN:

1104000

Other (OTH)

AF:

0.675

AC:

40461

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12324

24648

36971

49295

61619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20320

40640

60960

81280

101600

<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:

0.597

AC:

90662

AN:

151980

Hom.:

29596

Cov.:

AF XY:

0.586

AC XY:

43523

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.384

AC:

15895

AN:

41438

American (AMR)

AF:

0.479

AC:

7315

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1472

AN:

3468

East Asian (EAS)

AF:

0.442

AC:

2277

AN:

5154

South Asian (SAS)

AF:

0.445

AC:

2141

AN:

4814

European-Finnish (FIN)

AF:

0.747

AC:

7885

AN:

10550

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.761

AC:

51742

AN:

67976

Other (OTH)

AF:

0.532

AC:

1120

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1626

3251

4877

6502

8128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.622

Hom.:

20534

Bravo

AF:

0.571

Asia WGS

AF:

0.443

AC:

1540

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

Lactose intolerance

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital lactase deficiency

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

-0.85

CADD

Benign

2.4

(source)

DANN

Benign

0.62

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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