Genetic Variant CLEC1A:p.Gly26Val (chr12-10098846-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016511.4(CLEC1A):c.77G>T(p.Gly26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G26A) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLEC1A
NM_016511.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

42 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06546044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC1A	NM_016511.4	MANE Select	c.77G>T	p.Gly26Val	missense	Exon 1 of 6	NP_057595.2
CLEC1A	NM_001297748.2		c.77G>T	p.Gly26Val	missense	Exon 1 of 5	NP_001284677.1	E9PFB4
CLEC1A	NM_001297749.2		c.77G>T	p.Gly26Val	missense	Exon 1 of 4	NP_001284678.1	E7ESV9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLEC1A	ENST00000315330.8	TSL:1 MANE Select	c.77G>T	p.Gly26Val	missense	Exon 1 of 6	ENSP00000326407.4	Q8NC01
CLEC1A	ENST00000902292.1		c.77G>T	p.Gly26Val	missense	Exon 1 of 7	ENSP00000572351.1
CLEC1A	ENST00000457018.6	TSL:2	c.77G>T	p.Gly26Val	missense	Exon 1 of 5	ENSP00000415048.2	E9PFB4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726764

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111622

Other (OTH)

AF:

0.00

AC:

AN:

60368

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

18390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.16

M_CAP

Benign

0.0046

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.15

REVEL

Benign

0.084

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.10

MutPred

0.18

Gain of catalytic residue at G26 (P = 0.0244)

MVP

0.45

MPC

0.042

ClinPred

0.18

GERP RS

4.7

PromoterAI

-0.0050

Neutral

(source)

Varity_R

0.063

gMVP

0.20

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over