2-135795612-A-T

Variant names:

• chr2-135795612-A-T
• rs1030766
• NM_002299.4:c.4977-837T>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.4977-837T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 135,816 control chromosomes in the GnomAD database, including 29,801 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 0.67 (29801 hom., cov: 29)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4	c.4977-837T>A		intron_variant	Intron 13 of 16	ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3	c.4977-837T>A		intron_variant	Intron 13 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.4977-837T>A		intron_variant	Intron 13 of 16	1	NM_002299.4	ENSP00000264162.2
LCT	ENST00000452974.1	n.*58-837T>A		intron_variant	Intron 6 of 6	1		ENSP00000391231.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 90856 AN: 135790 Hom.: 29787 Cov.: 29

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.669 AC: 90892 AN: 135816 Hom.: 29801 Cov.: 29 AF XY: 0.663 AC XY: 43671 AN XY: 65820

African (AFR) AF: 0.490 AC: 16950 AN: 34622

American (AMR) AF: 0.582 AC: 7315 AN: 12578

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1445 AN: 3064

East Asian (EAS) AF: 0.573 AC: 2240 AN: 3912

South Asian (SAS) AF: 0.597 AC: 2269 AN: 3802

European-Finnish (FIN) AF: 0.792 AC: 7485 AN: 9452

Middle Eastern (MID) AF: 0.436 AC: 96 AN: 220

European-Non Finnish (NFE) AF: 0.784 AC: 51263 AN: 65424

Other (OTH) AF: 0.599 AC: 1116 AN: 1864

Alfa AF: 0.658 Hom.: 2568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.16
PhyloP100		0.061
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: rs1030766; hg19: chr2-136553182;