11-47590227-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031909.3(C1QTNF4):​c.584G>A​(p.Gly195Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000651 in 1,382,520 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. 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. G195V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: C1QTNF4 NM_031909.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17756209).

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>A	p.Gly195Glu	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>A	p.Gly195Glu	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
	C1QTNF4	ENST00000862513.1		c.584G>A	p.Gly195Glu	missense	Exon 3 of 3	ENSP00000532572.1
	C1QTNF4	ENST00000954826.1		c.584G>A	p.Gly195Glu	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000651 AC: 9 AN: 1382520 Hom.: 0 Cov.: 32 AF XY: 0.0000103 AC XY: 7 AN XY: 682598

African (AFR) AF: 0.0000323 AC: 1 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: 0.00 AC: 0 AN: 75584

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: 0.00000741 AC: 8 AN: 1079618

Other (OTH) AF: 0.00 AC: 0 AN: 57212

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.1
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.19	N
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.85
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.050	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Benign	0.76	T
Polyphen		0.11	B
Vest4		0.15
MutPred		0.44		Gain of solvent accessibility (P = 0.0074)
MVP		0.27
ClinPred		0.16	T
GERP RS		2.8
Varity_R		0.068
gMVP		0.35
Mutation Taster		=95/5	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;