Variant 2-135836588-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000264162.7(LCT):c.582C>T(p.Thr194=) 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
ENST00000264162.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0840

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=-0.84).

BP6

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

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/exons	MANE	Protein	UniProt
LCT	NM_002299.4 linkuse as main transcript	c.582C>T	p.Thr194=	synonymous_variant	1/17	ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3 linkuse as main transcript	c.582C>T	p.Thr194=	synonymous_variant	1/15		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 linkuse as main transcript	c.582C>T	p.Thr194=	synonymous_variant	1/17	1	NM_002299.4	ENSP00000264162	P1

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

GnomAD3 exomes

AF:

0.549

AC:

138019

AN:

251478

Hom.:

43334

AF XY:

0.552

AC XY:

75054

AN XY:

135912

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 SAS exome

AF:

0.413

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

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.383

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.707

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.509

AC:

77360

AN:

151944

Hom.:

23867

Cov.:

AF XY:

0.500

AC XY:

37147

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.356

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.711

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.598

Hom.:

17709

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Lactose intolerance

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.2

DANN

Benign

0.55

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