rs872151

Variant names:

• chr2-135799235-C-T
• rs872151
• NM_002299.4:c.4867-1097G>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.4867-1097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,996 control chromosomes in the GnomAD database, including 2,488 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 0.16 (2488 hom., cov: 31)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4	c.4867-1097G>A		intron_variant	Intron 12 of 16	ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3	c.4867-1097G>A		intron_variant	Intron 12 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.4867-1097G>A		intron_variant	Intron 12 of 16	1	NM_002299.4	ENSP00000264162.2
LCT	ENST00000452974.1	n.2960-1097G>A		intron_variant	Intron 5 of 6	1		ENSP00000391231.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24764 AN: 151878 Hom.: 2489 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.163 AC: 24786 AN: 151996 Hom.: 2488 Cov.: 31 AF XY: 0.172 AC XY: 12768 AN XY: 74282

African (AFR) AF: 0.204 AC: 8464 AN: 41456

American (AMR) AF: 0.252 AC: 3843 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 681 AN: 3462

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5156

South Asian (SAS) AF: 0.367 AC: 1765 AN: 4806

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10564

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 7017 AN: 67968

Other (OTH) AF: 0.191 AC: 403 AN: 2106

Alfa AF: 0.156 Hom.: 350

Bravo AF: 0.169

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		-0.92
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: rs872151; hg19: chr2-136556805;