rs1042712

chr2-135788274-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002299.4(LCT):c.*50G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,361,456 control chromosomes in the GnomAD database, including 477,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47297 hom., cov: 32)
  • Exomes 𝑓: 0.84 (430522 hom.)
• Consequence: LCT NM_002299.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.108

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-135788274-C-G is Benign according to our data. Variant chr2-135788274-C-G is described in ClinVar as [Benign]. Clinvar id is 331159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.*50G>C		3_prime_UTR_variant	17/17	ENST00000264162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.*50G>C		3_prime_UTR_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119278 AN: 152034 Hom.: 47267 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.729

GnomAD3 exomes AF: 0.796 AC: 195021 AN: 244904 Hom.: 78796 AF XY: 0.792 AC XY: 105287 AN XY: 132878

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.808

Gnomad ASJ exome AF: 0.543

Gnomad EAS exome AF: 0.808

Gnomad SAS exome AF: 0.743

Gnomad FIN exome AF: 0.863

Gnomad NFE exome AF: 0.833

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.839 AC: 1015133 AN: 1209306 Hom.: 430522 Cov.: 17 AF XY: 0.833 AC XY: 511533 AN XY: 613866

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.785 AC: 119363 AN: 152150 Hom.: 47297 Cov.: 32 AF XY: 0.782 AC XY: 58170 AN XY: 74372

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.726

Alfa AF: 0.768 Hom.: 8447

Bravo AF: 0.774

Asia WGS AF: 0.777 AC: 2701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Lactose intolerance Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.72
Dann	Benign	0.32

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: rs1042712; hg19: chr2-136545844;