rs2322813

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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-AS1 (HGNC:40337): (LCT antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.805-1236T>C		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.805-1236T>C		intron	N/A	ENSP00000264162.2
	LCT-AS1	ENST00000769912.1		n.401-4167A>G		intron	N/A

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

African (AFR) AF: 0.142 AC: 5908 AN: 41480

American (AMR) AF: 0.234 AC: 3577 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3464

East Asian (EAS) AF: 0.163 AC: 841 AN: 5166

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4814

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10572

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11237 AN: 67976

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.175 Hom.: 349

Bravo AF: 0.178

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.64
PhyloP100		0.17
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: rs2322813; hg19: chr2-136582809;