chr12-8125585-A-T

Variant names:

• chr12-8125585-A-T
• rs2024301
• NM_016184.4:c.107A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016184.4(CLEC4A):​c.107A>T​(p.His36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,608,236 control chromosomes in the GnomAD database, including 337,036 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25746 hom., cov: 31)
  • Exomes 𝑓: 0.65 (311290 hom.)
• Consequence: CLEC4A NM_016184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 40 publications found

Genes affected

CLEC4A (HGNC:13257): (C-type lectin domain family 4 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 signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. 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]

ENSG00000284697 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0386118E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC4A	NM_016184.4	c.107A>T	p.His36Leu	missense_variant	Exon 2 of 6	ENST00000229332.12	NP_057268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC4A	ENST00000229332.12	c.107A>T	p.His36Leu	missense_variant	Exon 2 of 6	1	NM_016184.4	ENSP00000229332.5

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86302 AN: 151878 Hom.: 25737 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.616

GnomAD2 exomes AF: 0.592 AC: 148661 AN: 251092 AF XY: 0.599

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.530

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.649 AC: 945497 AN: 1456240 Hom.: 311290 Cov.: 33 AF XY: 0.646 AC XY: 468426 AN XY: 724728

African (AFR) AF: 0.390 AC: 13003 AN: 33378

American (AMR) AF: 0.470 AC: 21020 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 16929 AN: 26102

East Asian (EAS) AF: 0.561 AC: 22246 AN: 39632

South Asian (SAS) AF: 0.525 AC: 45252 AN: 86114

European-Finnish (FIN) AF: 0.636 AC: 33944 AN: 53372

Middle Eastern (MID) AF: 0.641 AC: 3685 AN: 5752

European-Non Finnish (NFE) AF: 0.679 AC: 751413 AN: 1106990

Other (OTH) AF: 0.631 AC: 38005 AN: 60222

GnomAD4 genome AF: 0.568 AC: 86361 AN: 151996 Hom.: 25746 Cov.: 31 AF XY: 0.565 AC XY: 41925 AN XY: 74264

African (AFR) AF: 0.390 AC: 16180 AN: 41444

American (AMR) AF: 0.535 AC: 8171 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3472

East Asian (EAS) AF: 0.529 AC: 2734 AN: 5166

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4818

European-Finnish (FIN) AF: 0.619 AC: 6544 AN: 10570

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45846 AN: 67948

Other (OTH) AF: 0.611 AC: 1287 AN: 2108

Alfa AF: 0.646 Hom.: 10443

Bravo AF: 0.554

TwinsUK AF: 0.682 AC: 2530

ALSPAC AF: 0.693 AC: 2669

ESP6500AA AF: 0.404 AC: 1778

ESP6500EA AF: 0.674 AC: 5797

ExAC AF: 0.597 AC: 72467

Asia WGS AF: 0.506 AC: 1761 AN: 3478

EpiCase AF: 0.668

EpiControl AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.3
DANN	Benign	0.48
DEOGEN2	Benign	0.057	T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.30	T;T;T
MetaRNN	Benign	0.000010	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L;L;.
PhyloP100		0.17
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Benign	0.081
Sift	Benign	0.067	T;T;.
Sift4G	Uncertain	0.017	D;D;.
Polyphen		0.96	D;D;.
Vest4		0.18
MPC		0.26
ClinPred		0.052	T
GERP RS		-1.3
Varity_R		0.12
gMVP		0.42
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

Other links and lift over

dbSNP: rs2024301; hg19: chr12-8278181; COSMIC: COSV57561481; COSMIC: COSV57561481;