2-135799749-C-T

Variant names:

• chr2-135799749-C-T
• rs2322660
• NM_002299.4:c.4866+858G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002299.4(LCT):​c.4866+858G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,084 control chromosomes in the GnomAD database, including 24,515 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 0.52 (24515 hom., cov: 32)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• congenital lactase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002299.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.4866+858G>A		intron	N/A	NP_002290.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.4866+858G>A		intron	N/A	ENSP00000264162.2
	LCT	ENST00000452974.1	TSL:1	n.2960-1611G>A		intron	N/A	ENSP00000391231.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79624 AN: 151966 Hom.: 24514 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.524 AC: 79646 AN: 152084 Hom.: 24515 Cov.: 32 AF XY: 0.515 AC XY: 38270 AN XY: 74344

African (AFR) AF: 0.259 AC: 10736 AN: 41460

American (AMR) AF: 0.419 AC: 6414 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1077 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1999 AN: 5174

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4818

European-Finnish (FIN) AF: 0.711 AC: 7515 AN: 10574

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48327 AN: 67980

Other (OTH) AF: 0.455 AC: 960 AN: 2112

Alfa AF: 0.582 Hom.: 57775

Bravo AF: 0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.37
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2322660; hg19: chr2-136557319;