Variant rs2304370 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.4465-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,544,742 control chromosomes in the GnomAD database, including 31,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4869 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27096 hom. )

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.33

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=-0.84).

BP6

Variant 2-135804165-G-A is Benign according to our data. Variant chr2-135804165-G-A is described in ClinVar as [Benign]. Clinvar id is 1175392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 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.4465-37C>T		intron_variant		ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3 linkuse as main transcript	c.4465-37C>T		intron_variant			XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 linkuse as main transcript	c.4465-37C>T		intron_variant		1	NM_002299.4	ENSP00000264162	P1
LCT	ENST00000452974.1 linkuse as main transcript	c.2761-37C>T		intron_variant, NMD_transcript_variant		1		ENSP00000391231

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36253

AN:

151974

Hom.:

4868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.226

AC:

56199

AN:

248480

Hom.:

7589

AF XY:

0.230

AC XY:

30867

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.215

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.177

AC:

246483

AN:

1392650

Hom.:

27096

Cov.:

AF XY:

0.183

AC XY:

127667

AN XY:

696874

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.239

AC:

36278

AN:

152092

Hom.:

4869

Cov.:

AF XY:

0.239

AC XY:

17779

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.227

Hom.:

2716

Bravo

AF:

0.247

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	- -

Congenital lactase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.69

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