rs745500

Variant names:

• chr2-135825622-G-A
• rs745500
• NM_002299.4:c.805-1619C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002299.4(LCT):​c.805-1619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,058 control chromosomes in the GnomAD database, including 24,074 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 0.51 (24074 hom., cov: 31)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 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.805-1619C>T		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.805-1619C>T		intron	N/A	ENSP00000264162.2
	LCT-AS1	ENST00000769912.1		n.401-3784G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77758 AN: 151940 Hom.: 24073 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.511 AC: 77761 AN: 152058 Hom.: 24074 Cov.: 31 AF XY: 0.503 AC XY: 37364 AN XY: 74306

African (AFR) AF: 0.217 AC: 8987 AN: 41490

American (AMR) AF: 0.415 AC: 6340 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5162

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4812

European-Finnish (FIN) AF: 0.711 AC: 7523 AN: 10578

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48291 AN: 67954

Other (OTH) AF: 0.447 AC: 943 AN: 2108

Alfa AF: 0.609 Hom.: 43959

Bravo AF: 0.480

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.69
PhyloP100		2.6
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: rs745500; hg19: chr2-136583192;