chr2-135822690-T-A

Position:

• chr2-135822690-T-A

Variant summary

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

The NM_002299.4(LCT):​c.908-592A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 157,946 control chromosomes in the GnomAD database, including 18,864 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 0.45 (18424 hom., cov: 33)
  • Exomes 𝑓: 0.34 (440 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCT	NM_002299.4	c.908-592A>T		intron_variant		ENST00000264162.7	NP_002290.2
LCT-AS1	NR_045486.1	n.1465T>A		non_coding_transcript_exon_variant	2/2
LCT	XM_017004088.3	c.908-592A>T		intron_variant			XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.908-592A>T		intron_variant		1	NM_002299.4	ENSP00000264162	P1
LCT-AS1	ENST00000437007.1	n.1465T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68733 AN: 152020 Hom.: 18388 Cov.: 33

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.337 AC: 1955 AN: 5808 Hom.: 440 Cov.: 0 AF XY: 0.350 AC XY: 1053 AN XY: 3006

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.452 AC: 68828 AN: 152138 Hom.: 18424 Cov.: 33 AF XY: 0.462 AC XY: 34360 AN XY: 74366

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.527

Alfa AF: 0.242 Hom.: 573

Bravo AF: 0.478

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.74

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: rs7579771; hg19: chr2-136580260;