2-135822717-T-C

Position:

• chr2-135822717-T-C

Variant summary

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

The NM_002299.4(LCT):​c.908-619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 156,696 control chromosomes in the GnomAD database, including 25,063 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 (24092 hom., cov: 32)
  • Exomes 𝑓: 0.62 (971 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCT	NM_002299.4	c.908-619A>G		intron_variant		ENST00000264162.7	NP_002290.2
LCT-AS1	NR_045486.1	n.1492T>C		non_coding_transcript_exon_variant	2/2
LCT	XM_017004088.3	c.908-619A>G		intron_variant			XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.908-619A>G		intron_variant		1	NM_002299.4	ENSP00000264162	P1
LCT-AS1	ENST00000437007.1	n.1492T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77882 AN: 152036 Hom.: 24091 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.619 AC: 2813 AN: 4542 Hom.: 971 Cov.: 0 AF XY: 0.607 AC XY: 1399 AN XY: 2306

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.512 AC: 77891 AN: 152154 Hom.: 24092 Cov.: 32 AF XY: 0.503 AC XY: 37438 AN XY: 74374

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.447

Alfa AF: 0.623 Hom.: 12478

Bravo AF: 0.481

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.86

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: rs2164210; hg19: chr2-136580287;