Genetic Variant NM_002299.4:c.*595T>C (chr2-135787729-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002299.4(LCT):c.*595T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 156,138 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.050 ( 345 hom., cov: 32)

Exomes 𝑓: 0.013 ( 1 hom. )

Consequence

LCT
NM_002299.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.*595T>C		downstream_gene_variant		ENST00000264162.7	NP_002290.2	P09848

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 link	c.*595T>C		downstream_gene_variant		1	NM_002299.4	ENSP00000264162.2		P09848

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7580

AN:

152118

Hom.:

346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0324

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0407

GnomAD4 exome

AF:

0.0131

AC:

AN:

3902

Hom.:

AF XY:

0.0141

AC XY:

AN XY:

2064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0500

Gnomad4 SAS exome

AF:

0.00995

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00725

GnomAD4 genome

AF:

0.0498

AC:

7587

AN:

152236

Hom.:

345

Cov.:

AF XY:

0.0485

AC XY:

3612

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.0592

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0224

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0286

Hom.:

182

Bravo

AF:

0.0538

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

DANN

Benign

0.43

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over