rs2236783

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.582C>T(p.Thr194Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,296 control chromosomes in the GnomAD database, including 393,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23867 hom., cov: 31)

Exomes 𝑓: 0.69 ( 370010 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0840

Publications

33 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=-0.84).

BP6

Variant 2-135836588-G-A is Benign according to our data. Variant chr2-135836588-G-A is described in ClinVar as Benign. ClinVar VariationId is 331210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.084 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.582C>T	p.Thr194Thr	synonymous_variant	Exon 1 of 17	ENST00000264162.7	NP_002290.2	P09848
LCT	XM_017004088.3 link	c.582C>T	p.Thr194Thr	synonymous_variant	Exon 1 of 15		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 link	c.582C>T	p.Thr194Thr	synonymous_variant	Exon 1 of 17	1	NM_002299.4	ENSP00000264162.2		P09848

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77346

AN:

151828

Hom.:

23865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.448

GnomAD2 exomes

AF:

0.549

AC:

138019

AN:

251478

AF XY:

0.552

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.709

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.688

AC:

1006069

AN:

1461352

Hom.:

370010

Cov.:

AF XY:

0.677

AC XY:

492412

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.196

AC:

6548

AN:

33470

American (AMR)

AF:

0.400

AC:

17906

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

7944

AN:

26136

East Asian (EAS)

AF:

0.383

AC:

15195

AN:

39698

South Asian (SAS)

AF:

0.419

AC:

36143

AN:

86236

European-Finnish (FIN)

AF:

0.707

AC:

37755

AN:

53418

Middle Eastern (MID)

AF:

0.246

AC:

1417

AN:

5766

European-Non Finnish (NFE)

AF:

0.761

AC:

846069

AN:

1111528

Other (OTH)

AF:

0.614

AC:

37092

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16543

33086

49628

66171

82714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20040

40080

60120

80160

100200

<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:

0.509

AC:

77360

AN:

151944

Hom.:

23867

Cov.:

AF XY:

0.500

AC XY:

37147

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.222

AC:

9195

AN:

41428

American (AMR)

AF:

0.388

AC:

5919

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1068

AN:

3470

East Asian (EAS)

AF:

0.356

AC:

1828

AN:

5142

South Asian (SAS)

AF:

0.381

AC:

1836

AN:

4814

European-Finnish (FIN)

AF:

0.711

AC:

7508

AN:

10554

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48298

AN:

67958

Other (OTH)

AF:

0.443

AC:

934

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1513

3026

4538

6051

7564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.566

Hom.:

26897

Bravo

AF:

0.475

Asia WGS

AF:

0.381

AC:

1327

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2021

GeneDx

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

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

(source)

DANN

Benign

0.55

PhyloP100

-0.084

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over