Variant chr2-135788274-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002299.4(LCT):c.*50G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,361,456 control chromosomes in the GnomAD database, including 477,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47297 hom., cov: 32)

Exomes 𝑓: 0.84 ( 430522 hom. )

Consequence

LCT
NM_002299.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.108

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-135788274-C-G is Benign according to our data. Variant chr2-135788274-C-G is described in ClinVar as [Benign]. Clinvar id is 331159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	17/17	ENST00000264162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119278

AN:

152034

Hom.:

47267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.711

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.869

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.729

GnomAD3 exomes

AF:

0.796

AC:

195021

AN:

244904

Hom.:

78796

AF XY:

0.792

AC XY:

105287

AN XY:

132878

show subpopulations

Gnomad AFR exome

AF:

0.706

Gnomad AMR exome

AF:

0.808

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.808

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.833

Gnomad OTH exome

AF:

0.765

GnomAD4 exome

AF:

0.839

AC:

1015133

AN:

1209306

Hom.:

430522

Cov.:

AF XY:

0.833

AC XY:

511533

AN XY:

613866

show subpopulations

Gnomad4 AFR exome

AF:

0.693

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.549

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.746

Gnomad4 FIN exome

AF:

0.862

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.802

GnomAD4 genome

AF:

0.785

AC:

119363

AN:

152150

Hom.:

47297

Cov.:

AF XY:

0.782

AC XY:

58170

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.748

Gnomad4 FIN

AF:

0.869

Gnomad4 NFE

AF:

0.840

Gnomad4 OTH

AF:

0.726

Alfa

AF:

0.768

Hom.:

8447

Bravo

AF:

0.774

Asia WGS

AF:

0.777

AC:

2701

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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

-0.88

CADD

Benign

0.72

DANN

Benign

0.32

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