2-135825124-T-C

Variant names:

• chr2-135825124-T-C
• rs730005
• NM_002299.4:c.805-1121A>G

Variant summary

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

The NM_002299.4(LCT):​c.805-1121A>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
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 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.805-1121A>G		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.805-1121A>G		intron	N/A	ENSP00000264162.2
	LCT-AS1	ENST00000769912.1		n.401-4282T>C		intron	N/A

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

African (AFR) AF: 0.197 AC: 8176 AN: 41540

American (AMR) AF: 0.240 AC: 3666 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1578 AN: 3466

East Asian (EAS) AF: 0.163 AC: 844 AN: 5180

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10606

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

European-Non Finnish (NFE) AF: 0.165 AC: 11247 AN: 68026

Other (OTH) AF: 0.261 AC: 551 AN: 2112

Alfa AF: 0.165 Hom.: 1321

Bravo AF: 0.196

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-0.49
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: rs730005; hg19: chr2-136582694;