2-135796069-G-A

Variant names:

• chr2-135796069-G-A
• rs1011361
• NM_002299.4:c.4977-1294C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 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.4977-1294C>T		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.4977-1294C>T		intron	N/A	ENSP00000264162.2
	LCT	ENST00000452974.1	TSL:1	n.*58-1294C>T		intron	N/A	ENSP00000391231.1

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

African (AFR) AF: 0.221 AC: 9160 AN: 41464

American (AMR) AF: 0.439 AC: 6704 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1972 AN: 5160

South Asian (SAS) AF: 0.386 AC: 1860 AN: 4816

European-Finnish (FIN) AF: 0.734 AC: 7758 AN: 10570

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49775 AN: 67968

Other (OTH) AF: 0.476 AC: 1007 AN: 2114

Alfa AF: 0.594 Hom.: 12864

Bravo AF: 0.496

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.33
PhyloP100		-0.23
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: rs1011361; hg19: chr2-136553639;