chr2-135817629-G-T

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.1419C>A(p.Gly473Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,613,654 control chromosomes in the GnomAD database, including 395,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G473G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.51 ( 24069 hom., cov: 33)

Exomes 𝑓: 0.69 ( 371243 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.54

Publications

25 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=-0.86).

BP6

Variant 2-135817629-G-T is Benign according to our data. Variant chr2-135817629-G-T is described in ClinVar as Benign. ClinVar VariationId is 331202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.54 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.1419C>A	p.Gly473Gly	synonymous_variant	Exon 6 of 17	ENST00000264162.7	NP_002290.2	P09848
LCT	XM_017004088.3 link	c.1419C>A	p.Gly473Gly	synonymous_variant	Exon 6 of 15		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 link	c.1419C>A	p.Gly473Gly	synonymous_variant	Exon 6 of 17	1	NM_002299.4	ENSP00000264162.2		P09848

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77763

AN:

152018

Hom.:

24068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.450

GnomAD2 exomes

AF:

0.558

AC:

140065

AN:

250814

AF XY:

0.559

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.710

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.691

AC:

1009374

AN:

1461518

Hom.:

371243

Cov.:

AF XY:

0.679

AC XY:

493777

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.188

AC:

6295

AN:

33472

American (AMR)

AF:

0.456

AC:

20364

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

7997

AN:

26136

East Asian (EAS)

AF:

0.426

AC:

16905

AN:

39696

South Asian (SAS)

AF:

0.416

AC:

35882

AN:

86254

European-Finnish (FIN)

AF:

0.707

AC:

37671

AN:

53268

Middle Eastern (MID)

AF:

0.243

AC:

1402

AN:

5768

European-Non Finnish (NFE)

AF:

0.761

AC:

845744

AN:

1111832

Other (OTH)

AF:

0.615

AC:

37114

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16915

33829

50744

67658

84573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20072

40144

60216

80288

100360

<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:

0.511

AC:

77765

AN:

152136

Hom.:

24069

Cov.:

AF XY:

0.503

AC XY:

37360

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.217

AC:

8998

AN:

41522

American (AMR)

AF:

0.414

AC:

6335

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1073

AN:

3472

East Asian (EAS)

AF:

0.386

AC:

1989

AN:

5154

South Asian (SAS)

AF:

0.379

AC:

1828

AN:

4824

European-Finnish (FIN)

AF:

0.711

AC:

7507

AN:

10564

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48318

AN:

67998

Other (OTH)

AF:

0.446

AC:

942

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1543

3086

4629

6172

7715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.519

Hom.:

14394

Bravo

AF:

0.480

Asia WGS

AF:

0.387

AC:

1348

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

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.045

(source)

DANN

Benign

0.62

PhyloP100

-3.5

Mutation Taster

=95/5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over