Variant chr2-135788314-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002299.4(LCT):c.*10A>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 0.00307 in 1,597,068 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 20 hom. )

Consequence

LCT
NM_002299.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.712

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4 linkuse as main transcript	c.*10A>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.*10A>C		3_prime_UTR_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

562

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00406

AC:

1018

AN:

250490

Hom.:

AF XY:

0.00411

AC XY:

557

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00301

AC:

4349

AN:

1444792

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2193

AN XY:

720036

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.00261

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00368

AC:

561

AN:

152276

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lactose intolerance

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency

Uncertain:1

Uncertain significance, 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

0.69

DANN

Benign

0.40

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