Genetic Variant CLEC7A:c.*2A>G (chr12-10118456-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.959

Variant links:

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]

CLEC7A links:

LOC105369655 (HGNC:):

LOC105369655 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CLEC7A	NM_197947.3 link	c.*2A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000304084.13	NP_922938.1	Q9BXN2-1Q68D78A0A024RAN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC7A	ENST00000304084 link	c.*2A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_197947.3	ENSP00000302569.8		Q9BXN2-1

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124054

AN:

152042

Hom.:

51852

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.802

AC XY:

580007

AN XY:

723056

show subpopulations

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.:

AF XY:

0.805

AC XY:

59910

AN XY:

74394

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over