rs7959451

chr12-10118456-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_197947.3(CLEC7A):c.*2A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,604,602 control chromosomes in the GnomAD database, including 539,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51886 hom., cov: 32)
  • Exomes 𝑓: 0.81 (487304 hom.)
• Consequence: CLEC7A NM_197947.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.959

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

LOC105369655 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-10118456-T-C is Benign according to our data. Variant chr12-10118456-T-C is described in ClinVar as [Benign]. Clinvar id is 402543.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-10118456-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC7A	NM_197947.3	c.*2A>G		3_prime_UTR_variant	6/6	ENST00000304084.13
LOC105369655	XR_007063208.1	n.181+2913T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC7A	ENST00000304084.13	c.*2A>G		3_prime_UTR_variant	6/6	1	NM_197947.3	P4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124054 AN: 152042 Hom.: 51852 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.819

GnomAD3 exomes AF: 0.734 AC: 183479 AN: 250088 Hom.: 71739 AF XY: 0.733 AC XY: 99120 AN XY: 135292

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.888

Gnomad EAS exome AF: 0.310

Gnomad SAS exome AF: 0.531

Gnomad FIN exome AF: 0.827

Gnomad NFE exome AF: 0.854

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.809 AC: 1174451 AN: 1452442 Hom.: 487304 Cov.: 35 AF XY: 0.802 AC XY: 580007 AN XY: 723056

Gnomad4 AFR exome AF: 0.877

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.886

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.796

GnomAD4 genome AF: 0.816 AC: 124133 AN: 152160 Hom.: 51886 Cov.: 32 AF XY: 0.805 AC XY: 59910 AN XY: 74394

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.809

Alfa AF: 0.838 Hom.: 125623

Bravo AF: 0.811

Asia WGS AF: 0.421 AC: 1465 AN: 3478

EpiCase AF: 0.856

EpiControl AF: 0.852

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.52

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: rs7959451; hg19: chr12-10271055; COSMIC: COSV53721613; COSMIC: COSV53721613;