2-135795959-C-T

Variant names:

• chr2-135795959-C-T
• rs1030764
• NM_002299.4:c.4977-1184G>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.4977-1184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,946 control chromosomes in the GnomAD database, including 30,387 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 0.61 (30387 hom., cov: 31)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 0 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.4977-1184G>A		intron	N/A	NP_002290.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.4977-1184G>A		intron	N/A	ENSP00000264162.2	P09848
	LCT	ENST00000452974.1	TSL:1	n.*58-1184G>A		intron	N/A	ENSP00000391231.1	H0Y4E4

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92235 AN: 151828 Hom.: 30384 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.607 AC: 92269 AN: 151946 Hom.: 30387 Cov.: 31 AF XY: 0.599 AC XY: 44485 AN XY: 74258

African (AFR) AF: 0.387 AC: 16024 AN: 41426

American (AMR) AF: 0.509 AC: 7766 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1475 AN: 3466

East Asian (EAS) AF: 0.630 AC: 3250 AN: 5156

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4814

European-Finnish (FIN) AF: 0.749 AC: 7904 AN: 10550

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.761 AC: 51708 AN: 67960

Other (OTH) AF: 0.542 AC: 1142 AN: 2106

Alfa AF: 0.663 Hom.: 4361

Bravo AF: 0.585

Asia WGS AF: 0.511 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.35
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: rs1030764; hg19: chr2-136553529;