2-135788274-C-G

Variant names:

• chr2-135788274-C-G
• rs1042712
• NM_002299.4:c.*50G>C

Variant summary

Our verdict is Benign. The variant received -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:4
• 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LCT	NM_002299.4	c.*50G>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000264162.7	NP_002290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162	c.*50G>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_002299.4	ENSP00000264162.2

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

GnomAD2 exomes AF: 0.796 AC: 195021 AN: 244904 AF XY: 0.792

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 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 AC: 19865 AN: 28646

Gnomad4 AMR exome AF: 0.802 AC: 35626 AN: 44404

Gnomad4 ASJ exome AF: 0.549 AC: 13517 AN: 24628

Gnomad4 EAS exome AF: 0.822 AC: 31736 AN: 38610

Gnomad4 SAS exome AF: 0.746 AC: 60694 AN: 81344

Gnomad4 FIN exome AF: 0.862 AC: 39038 AN: 45262

Gnomad4 NFE exome AF: 0.865 AC: 770248 AN: 889956

Gnomad4 Remaining exome AF: 0.802 AC: 41810 AN: 52164

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 AC: 0.710879 AN: 0.710879

Gnomad4 AMR AF: 0.748 AC: 0.74784 AN: 0.74784

Gnomad4 ASJ AF: 0.547 AC: 0.546947 AN: 0.546947

Gnomad4 EAS AF: 0.802 AC: 0.802087 AN: 0.802087

Gnomad4 SAS AF: 0.748 AC: 0.747613 AN: 0.747613

Gnomad4 FIN AF: 0.869 AC: 0.869409 AN: 0.869409

Gnomad4 NFE AF: 0.840 AC: 0.839601 AN: 0.839601

Gnomad4 OTH AF: 0.726 AC: 0.725546 AN: 0.725546

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lactose intolerance Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital lactase deficiency Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.32
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

Publications

LitVar

Other links and lift over

dbSNP: rs1042712; hg19: chr2-136545844;