rs2322813

Variant names:

• chr2-135825239-A-G
• rs2322813
• NM_002299.4:c.805-1236T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002299.4(LCT):​c.805-1236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,054 control chromosomes in the GnomAD database, including 2,661 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 0.17 (2661 hom., cov: 32)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4	c.805-1236T>C		intron_variant	Intron 3 of 16	ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3	c.805-1236T>C		intron_variant	Intron 3 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.805-1236T>C		intron_variant	Intron 3 of 16	1	NM_002299.4	ENSP00000264162.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26492 AN: 151938 Hom.: 2660 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.174 AC: 26508 AN: 152054 Hom.: 2661 Cov.: 32 AF XY: 0.177 AC XY: 13132 AN XY: 74310

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.250

Alfa AF: 0.175 Hom.: 335

Bravo AF: 0.178

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2322813; hg19: chr2-136582809;