rs730005

chr2-135825124-T-Cchr2-135825124-T-G

Variant summary

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

The NM_002299.4(LCT):c.805-1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,242 control chromosomes in the GnomAD database, including 3,070 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 0.19 (3070 hom., cov: 33)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.805-1121A>G		intron_variant		ENST00000264162.7
LCT	XM_017004088.3	c.805-1121A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.805-1121A>G		intron_variant		1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28896 AN: 152124 Hom.: 3070 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.190 AC: 28913 AN: 152242 Hom.: 3070 Cov.: 33 AF XY: 0.192 AC XY: 14273 AN XY: 74450

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.261

Alfa AF: 0.162 Hom.: 1141

Bravo AF: 0.196

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.47
Dann	Benign	0.54

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: rs730005; hg19: chr2-136582694;