Variant rs3739022 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 NM_002299.4(LCT):c.4329C>T(p.Gly1443Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,826 control chromosomes in the GnomAD database, including 16,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2414 hom., cov: 32)

Exomes 𝑓: 0.12 ( 13993 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.48

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 2-135804902-G-A is Benign according to our data. Variant chr2-135804902-G-A is described in ClinVar as [Benign]. Clinvar id is 331176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135804902-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 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.4329C>T	p.Gly1443Gly	synonymous_variant	10/17	ENST00000264162.7	NP_002290.2	P09848
LCT	XM_017004088.3 linkuse as main transcript	c.4329C>T	p.Gly1443Gly	synonymous_variant	10/15		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 linkuse as main transcript	c.4329C>T	p.Gly1443Gly	synonymous_variant	10/17	1	NM_002299.4	ENSP00000264162.2		P09848
LCT	ENST00000452974.1 linkuse as main transcript	n.2625C>T		non_coding_transcript_exon_variant	4/7	1		ENSP00000391231.1		H0Y4E4

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24529

AN:

151962

Hom.:

2414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.0985

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.169

AC:

42525

AN:

251266

Hom.:

4628

AF XY:

0.171

AC XY:

23225

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.117

AC:

170360

AN:

1461746

Hom.:

13993

Cov.:

AF XY:

0.122

AC XY:

88927

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.0858

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.161

AC:

24560

AN:

152080

Hom.:

2414

Cov.:

AF XY:

0.170

AC XY:

12615

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0985

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.124

Hom.:

2900

Bravo

AF:

0.168

Asia WGS

AF:

0.295

AC:

1026

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

-0.76

CADD

Benign

0.052

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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