Variant chr12-10098846-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016511.4(CLEC1A):c.77G>C(p.Gly26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,612,902 control chromosomes in the GnomAD database, including 575,530 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54459 hom., cov: 31)

Exomes 𝑓: 0.83 ( 521071 hom. )

Consequence

CLEC1A
NM_016511.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

CLEC1A (HGNC:24355): (C-type lectin domain family 1 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The encoded protein may play a role in regulating dendritic cell function. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CLEC1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8313844E-7).

BP6

Variant 12-10098846-C-G is Benign according to our data. Variant chr12-10098846-C-G is described in ClinVar as [Benign]. Clinvar id is 590287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC1A	NM_016511.4 linkuse as main transcript	c.77G>C	p.Gly26Ala	missense_variant	1/6	ENST00000315330.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC1A	ENST00000315330.8 linkuse as main transcript	c.77G>C	p.Gly26Ala	missense_variant	1/6	1	NM_016511.4	P1

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

127161

AN:

152036

Hom.:

54423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.874

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.826

GnomAD3 exomes

AF:

0.753

AC:

188072

AN:

249870

Hom.:

75770

AF XY:

0.759

AC XY:

102515

AN XY:

135038

show subpopulations

Gnomad AFR exome

AF:

0.897

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.875

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.623

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.883

Gnomad OTH exome

AF:

0.805

GnomAD4 exome

AF:

0.834

AC:

1218965

AN:

1460748

Hom.:

521071

Cov.:

AF XY:

0.830

AC XY:

603306

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.902

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.872

Gnomad4 EAS exome

AF:

0.315

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.868

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.818

GnomAD4 genome

AF:

0.836

AC:

127241

AN:

152154

Hom.:

54459

Cov.:

AF XY:

0.828

AC XY:

61587

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.898

Gnomad4 AMR

AF:

0.686

Gnomad4 ASJ

AF:

0.874

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.874

Gnomad4 NFE

AF:

0.879

Gnomad4 OTH

AF:

0.819

Alfa

AF:

0.869

Hom.:

18390

Bravo

AF:

0.824

TwinsUK

AF:

0.876

AC:

3248

ALSPAC

AF:

0.871

AC:

3357

ESP6500AA

AF:

0.899

AC:

3961

ESP6500EA

AF:

0.879

AC:

7560

ExAC

AF:

0.765

AC:

92918

Asia WGS

AF:

0.483

AC:

1682

AN:

3478

EpiCase

AF:

0.878

EpiControl

AF:

0.876

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 29489751) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Aspergillosis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.7

DANN

Benign

0.68

DEOGEN2

Benign

0.0017

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

5.8e-7

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.95

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

B;B;B;.

Vest4

0.011

MPC

0.038

ClinPred

0.00079

GERP RS

4.7

Varity_R

0.028

gMVP

0.17

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