rs113848396

Variant names:

• chr12-7741484-A-C
• rs113848396
• NM_001371390.1:c.172T>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001371390.1(CLEC4C):​c.172T>G​(p.Leu58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,612,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CLEC4C NM_001371390.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.287
• Publications: 1 publications found

Genes affected

CLEC4C (HGNC:13258): (C-type lectin domain family 4 member C) 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 dendritic cell function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLEC4C Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054988563).
• BP6: Variant 12-7741484-A-C is Benign according to our data. Variant chr12-7741484-A-C is described in ClinVar as Benign. ClinVar VariationId is 727182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 297 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371390.1. 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
	CLEC4C	NM_001371390.1	MANE Select	c.172T>G	p.Leu58Val	missense	Exon 3 of 6	NP_001358319.1	Q8WTT0-1
	CLEC4C	NM_130441.3		c.172T>G	p.Leu58Val	missense	Exon 4 of 7	NP_569708.1	Q8WTT0-1
	CLEC4C	NM_203503.2		c.79T>G	p.Leu27Val	missense	Exon 3 of 6	NP_987099.1	Q8WTT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC4C	ENST00000360345.8	TSL:1 MANE Select	c.172T>G	p.Leu58Val	missense	Exon 3 of 6	ENSP00000353500.3	Q8WTT0-1
	CLEC4C	ENST00000542353.5	TSL:1	c.172T>G	p.Leu58Val	missense	Exon 4 of 7	ENSP00000440428.1	Q8WTT0-1
	CLEC4C	ENST00000540085.5	TSL:1	c.79T>G	p.Leu27Val	missense	Exon 2 of 5	ENSP00000445338.1	Q8WTT0-2

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 292 AN: 152190 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000529 AC: 133 AN: 251474 AF XY: 0.000419

Gnomad AFR exome AF: 0.00615

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000267 AC: 390 AN: 1460532 Hom.: 0 Cov.: 30 AF XY: 0.000227 AC XY: 165 AN XY: 726716

African (AFR) AF: 0.00804 AC: 269 AN: 33446

American (AMR) AF: 0.000581 AC: 26 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1110786

Other (OTH) AF: 0.000481 AC: 29 AN: 60350

GnomAD4 genome AF: 0.00195 AC: 297 AN: 152308 Hom.: 1 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74474

African (AFR) AF: 0.00649 AC: 270 AN: 41578

American (AMR) AF: 0.000851 AC: 13 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00212

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000610 AC: 74

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.00092	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.29
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.075
Sift	Benign	0.049	D
Sift4G	Benign	0.20	T
Polyphen		0.30	B
Vest4		0.17
MVP		0.15
MPC		0.40
ClinPred		0.0079	T
GERP RS		-1.4
Varity_R		0.040
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs113848396; hg19: chr12-7894080;