11-47590339-C-G

Variant names:

• chr11-47590339-C-G
• rs1040975912
• NM_031909.3:c.472G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031909.3(C1QTNF4):​c.472G>C​(p.Ala158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,341,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A158V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: C1QTNF4 NM_031909.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07480466).

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.472G>C	p.Ala158Pro	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.472G>C	p.Ala158Pro	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
	C1QTNF4	ENST00000862513.1		c.472G>C	p.Ala158Pro	missense	Exon 3 of 3	ENSP00000532572.1
	C1QTNF4	ENST00000954826.1		c.472G>C	p.Ala158Pro	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 39 AN: 148310 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000905

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000980

GnomAD4 exome AF: 0.00000754 AC: 9 AN: 1193272 Hom.: 0 Cov.: 31 AF XY: 0.00000693 AC XY: 4 AN XY: 577486

African (AFR) AF: 0.000357 AC: 8 AN: 22426

American (AMR) AF: 0.00 AC: 0 AN: 9720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15684

East Asian (EAS) AF: 0.00 AC: 0 AN: 25066

South Asian (SAS) AF: 0.00 AC: 0 AN: 53992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985958

Other (OTH) AF: 0.0000208 AC: 1 AN: 48154

GnomAD4 genome AF: 0.000263 AC: 39 AN: 148310 Hom.: 0 Cov.: 32 AF XY: 0.000249 AC XY: 18 AN XY: 72250

African (AFR) AF: 0.000905 AC: 37 AN: 40892

American (AMR) AF: 0.00 AC: 0 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66856

Other (OTH) AF: 0.000980 AC: 2 AN: 2040

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000204

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	0.067
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.17	N
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.2	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	2.1	N
REVEL	Benign	0.089
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.67		Gain of loop (P = 0.0166)
MVP		0.043
ClinPred		0.67	D
GERP RS		3.5
PromoterAI		-0.22	Neutral
Varity_R		0.16
gMVP		0.24
Mutation Taster		=68/32	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: rs1040975912; hg19: chr11-47611891;