12-8515301-A-G

Variant names:

• chr12-8515301-A-G
• rs4304840
• NM_080387.5:c.94A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080387.5(CLEC4D):​c.94A>G​(p.Ser32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,467,864 control chromosomes in the GnomAD database, including 45,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9433 hom., cov: 31)
  • Exomes 𝑓: 0.22 (36254 hom.)
• Consequence: CLEC4D NM_080387.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.165
• Publications: 38 publications found

Genes affected

CLEC4D (HGNC:14554): (C-type lectin domain family 4 member D) 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. 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.259169E-5).
• BP6: Variant 12-8515301-A-G is Benign according to our data. Variant chr12-8515301-A-G is described in ClinVar as Benign. ClinVar VariationId is 402542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080387.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4D	NM_080387.5	MANE Select	c.94A>G	p.Ser32Gly	missense	Exon 2 of 6	NP_525126.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4D	ENST00000299665.3	TSL:1 MANE Select	c.94A>G	p.Ser32Gly	missense	Exon 2 of 6	ENSP00000299665.2	Q8WXI8
	CLEC4D	ENST00000959647.1		c.94A>G	p.Ser32Gly	missense	Exon 2 of 6	ENSP00000629706.1
	CLEC4D	ENST00000382064.6	TSL:3	c.94A>G	p.Ser32Gly	missense	Exon 3 of 6	ENSP00000371496.2	A6NHA5

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47826 AN: 151746 Hom.: 9414 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.234 AC: 58438 AN: 249968 AF XY: 0.233

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.222 AC: 292122 AN: 1316000 Hom.: 36254 Cov.: 23 AF XY: 0.222 AC XY: 147034 AN XY: 662298

African (AFR) AF: 0.577 AC: 17264 AN: 29932

American (AMR) AF: 0.155 AC: 6885 AN: 44392

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6750 AN: 25092

East Asian (EAS) AF: 0.127 AC: 4959 AN: 39042

South Asian (SAS) AF: 0.230 AC: 19099 AN: 83204

European-Finnish (FIN) AF: 0.208 AC: 10949 AN: 52636

Middle Eastern (MID) AF: 0.405 AC: 2198 AN: 5426

European-Non Finnish (NFE) AF: 0.215 AC: 210661 AN: 980860

Other (OTH) AF: 0.241 AC: 13357 AN: 55416

GnomAD4 genome AF: 0.315 AC: 47903 AN: 151864 Hom.: 9433 Cov.: 31 AF XY: 0.313 AC XY: 23227 AN XY: 74238

African (AFR) AF: 0.563 AC: 23309 AN: 41388

American (AMR) AF: 0.221 AC: 3379 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3468

East Asian (EAS) AF: 0.141 AC: 730 AN: 5162

South Asian (SAS) AF: 0.230 AC: 1106 AN: 4812

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10574

Middle Eastern (MID) AF: 0.328 AC: 95 AN: 290

European-Non Finnish (NFE) AF: 0.225 AC: 15279 AN: 67892

Other (OTH) AF: 0.314 AC: 659 AN: 2100

Alfa AF: 0.250 Hom.: 21660

Bravo AF: 0.327

TwinsUK AF: 0.214 AC: 793

ALSPAC AF: 0.217 AC: 835

ESP6500AA AF: 0.549 AC: 2420

ESP6500EA AF: 0.231 AC: 1987

ExAC AF: 0.246 AC: 29918

Asia WGS AF: 0.209 AC: 726 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.242

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.56
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.000023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.019
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Polyphen		0.0030	B
Vest4		0.17
MPC		0.029
ClinPred		0.0041	T
GERP RS		-0.30
Varity_R		0.052
gMVP		0.23
Mutation Taster		=98/2	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: rs4304840; hg19: chr12-8667897; COSMIC: COSV55230143; COSMIC: COSV55230143;