rs1011361

Positions:

• chr2-135796069-G-A

Variant summary

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

The NM_002299.4(LCT):​c.4977-1294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,050 control chromosomes in the GnomAD database, including 25,529 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 0.53 (25529 hom., cov: 32)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.4977-1294C>T		intron_variant		ENST00000264162.7
LCT	XM_017004088.3	c.4977-1294C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.4977-1294C>T		intron_variant		1	NM_002299.4	P1
LCT	ENST00000452974.1	c.*58-1294C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80307 AN: 151932 Hom.: 25527 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.528 AC: 80312 AN: 152050 Hom.: 25529 Cov.: 32 AF XY: 0.519 AC XY: 38603 AN XY: 74312

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.476

Alfa AF: 0.632 Hom.: 9016

Bravo AF: 0.496

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.33

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: rs1011361; hg19: chr2-136553639;