chr2-135817629-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 331202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135817629-G-T is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.558

AC:

140065

AN:

250814

Hom.:

44250

AF XY:

0.559

AC XY:

75857

AN XY:

135650

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 SAS exome

AF:

0.410

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

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.707

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.511

AC:

77765

AN:

152136

Hom.:

24069

Cov.:

AF XY:

0.503

AC XY:

37360

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.309

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.711

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.572

Hom.:

14035

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

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over