2-135817629-G-T

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 (★★).

Frequency

Genomes: 𝑓 0.51 ( 24069 hom., cov: 33)
Exomes 𝑓: 0.69 ( 371243 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

2

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]

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
LCTNM_002299.4 linkc.1419C>A p.Gly473Gly synonymous_variant Exon 6 of 17 ENST00000264162.7 NP_002290.2 P09848
LCTXM_017004088.3 linkc.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
LCTENST00000264162.7 linkc.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.:
33
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.:
51
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.:
33
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
-
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

- -

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 v4.3

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.

Other links and lift over

dbSNP: rs6719488; hg19: chr2-136575199; COSMIC: COSV51548354; COSMIC: COSV51548354; API