rs2322812

Positions:

• chr2-135820470-A-G

Variant summary

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

The NM_002299.4(LCT):​c.986+1550T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,424 control chromosomes in the GnomAD database, including 2,425 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 0.16 (2422 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.986+1550T>C		intron_variant		ENST00000264162.7
LCT-AS1	NR_045486.1	n.280A>G		non_coding_transcript_exon_variant	1/2
LCT	XM_017004088.3	c.986+1550T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.986+1550T>C		intron_variant		1	NM_002299.4	P1
LCT-AS1	ENST00000437007.1	n.280A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24527 AN: 152064 Hom.: 2421 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.136 AC: 33 AN: 242 Hom.: 3 Cov.: 0 AF XY: 0.146 AC XY: 26 AN XY: 178

Gnomad4 AFR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.161 AC: 24559 AN: 152182 Hom.: 2422 Cov.: 32 AF XY: 0.169 AC XY: 12605 AN XY: 74400

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0984

Gnomad4 OTH AF: 0.185

Alfa AF: 0.137 Hom.: 205

Bravo AF: 0.168

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.65

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: rs2322812; hg19: chr2-136578040;