NM_031909.3:c.643G>A

Variant names:

• chr11-47590168-C-T
• rs200374127
• NM_031909.3:c.643G>A

Variant summary

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

The NM_031909.3(C1QTNF4):​c.643G>A​(p.Asp215Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000145 in 1,600,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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. D215A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: C1QTNF4 NM_031909.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 2 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=0.15834075).

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.643G>A	p.Asp215Asn	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.643G>A	p.Asp215Asn	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
	C1QTNF4	ENST00000862513.1		c.643G>A	p.Asp215Asn	missense	Exon 3 of 3	ENSP00000532572.1
	C1QTNF4	ENST00000954826.1		c.643G>A	p.Asp215Asn	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151420 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000136 AC: 30 AN: 220242 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000628

Gnomad ASJ exome AF: 0.000323

Gnomad EAS exome AF: 0.0000599

Gnomad FIN exome AF: 0.000164

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000183

GnomAD4 exome AF: 0.000145 AC: 210 AN: 1449452 Hom.: 1 Cov.: 32 AF XY: 0.000136 AC XY: 98 AN XY: 721072

African (AFR) AF: 0.00 AC: 0 AN: 33058

American (AMR) AF: 0.0000466 AC: 2 AN: 42890

Ashkenazi Jewish (ASJ) AF: 0.000426 AC: 11 AN: 25818

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39356

South Asian (SAS) AF: 0.000199 AC: 17 AN: 85292

European-Finnish (FIN) AF: 0.000101 AC: 5 AN: 49312

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1108166

Other (OTH) AF: 0.000217 AC: 13 AN: 59824

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151420 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73886

African (AFR) AF: 0.0000242 AC: 1 AN: 41288

American (AMR) AF: 0.000197 AC: 3 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67832

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000412 Hom.: 0

Bravo AF: 0.000208

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000369 AC: 3

ExAC AF: 0.000151 AC: 18

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	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.077
FATHMM_MKL	Benign	0.60	D
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-0.46	N
PhyloP100		4.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.90	N
REVEL	Benign	0.27
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.16	B
Vest4		0.16
MVP		0.39
ClinPred		0.071	T
GERP RS		4.3
Varity_R		0.088
gMVP		0.39
Mutation Taster		=81/19	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: rs200374127; hg19: chr11-47611720;