chr11-47590227-C-A

Variant names:

• chr11-47590227-C-A
• rs780620024
• NM_031909.3:c.584G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031909.3(C1QTNF4):​c.584G>T​(p.Gly195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,532,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: C1QTNF4 NM_031909.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.850
• Publications: 0 publications found

Genes affected

C1QTNF4 (HGNC:14346): (C1q and TNF related 4) Predicted to enable cytokine activity. Involved in positive regulation of cytokine production and positive regulation of signal transduction. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040248245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031909.3. 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
	C1QTNF4	NM_031909.3	MANE Select	c.584G>T	p.Gly195Val	missense	Exon 2 of 2	NP_114115.2	Q9BXJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF4	ENST00000302514.4	TSL:1 MANE Select	c.584G>T	p.Gly195Val	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
	C1QTNF4	ENST00000862513.1		c.584G>T	p.Gly195Val	missense	Exon 3 of 3	ENSP00000532572.1
	C1QTNF4	ENST00000954826.1		c.584G>T	p.Gly195Val	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes AF: 0.000260 AC: 39 AN: 150230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000898

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.0000901 AC: 13 AN: 144232 AF XY: 0.000124

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 52 AN: 1382522 Hom.: 0 Cov.: 32 AF XY: 0.0000439 AC XY: 30 AN XY: 682600

African (AFR) AF: 0.00133 AC: 41 AN: 30940

American (AMR) AF: 0.00 AC: 0 AN: 33158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22390

East Asian (EAS) AF: 0.00 AC: 0 AN: 37678

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5204

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079618

Other (OTH) AF: 0.000140 AC: 8 AN: 57212

GnomAD4 genome AF: 0.000259 AC: 39 AN: 150340 Hom.: 0 Cov.: 32 AF XY: 0.000272 AC XY: 20 AN XY: 73430

African (AFR) AF: 0.000895 AC: 37 AN: 41344

American (AMR) AF: 0.0000663 AC: 1 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67562

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000276

ExAC AF: 0.0000617 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.9
DANN	Benign	0.88
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.20	N
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.090	N
PhyloP100		0.85
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.15
Sift	Benign	0.50	T
Sift4G	Benign	0.63	T
Polyphen		0.11	B
Vest4		0.18
MutPred		0.47		Loss of catalytic residue at G195 (P = 0.0211)
MVP		0.34
ClinPred		0.018	T
GERP RS		2.8
Varity_R		0.085
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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: rs780620024; hg19: chr11-47611779;