Variant 2-135787895-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002299.4(LCT):c.*429A>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 0.011 in 195,960 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., cov: 32)

Exomes 𝑓: 0.010 ( 10 hom. )

Consequence

LCT
NM_002299.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0740

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=-0.83).

BP6

Variant 2-135787895-T-G is Benign according to our data. Variant chr2-135787895-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 331155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135787895-T-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0113 (1717/152242) while in subpopulation SAS AF= 0.0406 (196/4824). AF 95% confidence interval is 0.036. There are 21 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCT	NM_002299.4 linkuse as main transcript	c.*429A>C		3_prime_UTR_variant	17/17	ENST00000264162.7	NP_002290.2	P09848

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162 linkuse as main transcript	c.*429A>C		3_prime_UTR_variant	17/17	1	NM_002299.4	ENSP00000264162.2		P09848

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1713

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00581

Gnomad OTH

AF:

0.00957

GnomAD4 exome

AF:

0.0101

AC:

440

AN:

43718

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

297

AN XY:

23432

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00592

Gnomad4 ASJ exome

AF:

0.0161

Gnomad4 EAS exome

AF:

0.00105

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.00372

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00596

GnomAD4 genome

AF:

0.0113

AC:

1717

AN:

152242

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

857

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0406

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00581

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00868

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Lactose intolerance

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency

Benign:1

Likely 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

-0.83

CADD

Benign

4.1

DANN

Benign

0.80

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