rs2304371

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002299.4(LCT):c.4606C>T(p.Leu1536Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,613,694 control chromosomes in the GnomAD database, including 536,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 39129 hom., cov: 32)

Exomes 𝑓: 0.82 ( 497659 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.196

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=-0.73).

BP6

Variant 2-135803987-G-A is Benign according to our data. Variant chr2-135803987-G-A is described in ClinVar as [Benign]. Clinvar id is 331172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135803987-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.196 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.4606C>T	p.Leu1536Leu	synonymous_variant	Exon 11 of 17	ENST00000264162.7	NP_002290.2	P09848
LCT	XM_017004088.3 link	c.4606C>T	p.Leu1536Leu	synonymous_variant	Exon 11 of 15		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 link	c.4606C>T	p.Leu1536Leu	synonymous_variant	Exon 11 of 17	1	NM_002299.4	ENSP00000264162.2		P09848
LCT	ENST00000452974.1 link	n.2902C>T		non_coding_transcript_exon_variant	Exon 5 of 7	1		ENSP00000391231.1		H0Y4E4

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106404

AN:

151974

Hom.:

39124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.658

GnomAD3 exomes

AF:

0.758

AC:

190438

AN:

251288

Hom.:

74188

AF XY:

0.758

AC XY:

102927

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.765

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.819

AC:

1196747

AN:

1461602

Hom.:

497659

Cov.:

AF XY:

0.813

AC XY:

591292

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.458

Gnomad4 AMR exome

AF:

0.760

Gnomad4 ASJ exome

AF:

0.516

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.738

Gnomad4 FIN exome

AF:

0.837

Gnomad4 NFE exome

AF:

0.849

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.700

AC:

106457

AN:

152092

Hom.:

39129

Cov.:

AF XY:

0.702

AC XY:

52150

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.700

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.780

Gnomad4 SAS

AF:

0.746

Gnomad4 FIN

AF:

0.844

Gnomad4 NFE

AF:

0.813

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.739

Hom.:

50045

Bravo

AF:

0.682

ClinVar

Significance: Benign

Submissions summary: Benign:8

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

- -

Congenital lactase deficiency

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Lactose intolerance

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

-0.73

CADD

Benign

8.3

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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