2-135798612-T-C

Position:

• chr2-135798612-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002299.4(LCT):​c.4867-474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,224 control chromosomes in the GnomAD database, including 48,171 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 0.79 (48171 hom., cov: 33)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.4867-474A>G		intron_variant		ENST00000264162.7
LCT	XM_017004088.3	c.4867-474A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.4867-474A>G		intron_variant		1	NM_002299.4	P1
LCT	ENST00000452974.1	c.2960-474A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120497 AN: 152106 Hom.: 48133 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120586 AN: 152224 Hom.: 48171 Cov.: 33 AF XY: 0.791 AC XY: 58864 AN XY: 74438

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.729

Alfa AF: 0.796 Hom.: 76354

Bravo AF: 0.783

Asia WGS AF: 0.805 AC: 2799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs3769013; hg19: chr2-136556182;