rs2278544

Positions:

chr2-135788540-A-G

Variant summary

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

The NM_002299.4(LCT):c.5568T>C(p.Ala1856=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,603,220 control chromosomes in the GnomAD database, including 442,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 29596 hom., cov: 31)

Exomes 𝑓: 0.74 ( 413239 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.140

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=-0.85).

BP6

Variant 2-135788540-A-G is Benign according to our data. Variant chr2-135788540-A-G is described in ClinVar as [Benign]. Clinvar id is 331164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135788540-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 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.5568T>C	p.Ala1856=	synonymous_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.5568T>C	p.Ala1856=	synonymous_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90631

AN:

151862

Hom.:

29593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.621

AC:

156029

AN:

251154

Hom.:

52340

AF XY:

0.622

AC XY:

84402

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.466

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.752

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.739

AC:

1072495

AN:

1451240

Hom.:

413239

Cov.:

AF XY:

0.729

AC XY:

526552

AN XY:

722514

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.428

Gnomad4 EAS exome

AF:

0.476

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.802

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.597

AC:

90662

AN:

151980

Hom.:

29596

Cov.:

AF XY:

0.586

AC XY:

43523

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.761

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.666

Hom.:

19342

Bravo

AF:

0.571

Asia WGS

AF:

0.443

AC:

1540

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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

-0.85

CADD

Benign

2.4

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