rs229526

Variant names:

• chr22-37185382-G-C
• rs229526
• NM_031910.4:c.125C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-37185382-G-C
• chr22-37185382-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031910.4(C1QTNF6):​c.125C>G​(p.Pro42Arg) variant causes a missense change. The variant allele was found at a frequency of 0.218 in 1,613,258 control chromosomes in the GnomAD database, including 39,123 homozygotes. In-silico tool predicts 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. P42T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (3742 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35381 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 44 publications found

Genes affected

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

IL2RB-AS1 (HGNC:40300):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027126372).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF6	NM_031910.4	c.125C>G	p.Pro42Arg	missense_variant	Exon 2 of 3	ENST00000337843.7	NP_114116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF6	ENST00000337843.7	c.125C>G	p.Pro42Arg	missense_variant	Exon 2 of 3	1	NM_031910.4	ENSP00000338812.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33148 AN: 152006 Hom.: 3730 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.192 AC: 47993 AN: 250112 AF XY: 0.197

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0975

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.218 AC: 318018 AN: 1461136 Hom.: 35381 Cov.: 36 AF XY: 0.217 AC XY: 158046 AN XY: 726876

African (AFR) AF: 0.278 AC: 9313 AN: 33458

American (AMR) AF: 0.103 AC: 4617 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4995 AN: 26114

East Asian (EAS) AF: 0.0934 AC: 3706 AN: 39674

South Asian (SAS) AF: 0.209 AC: 18015 AN: 86184

European-Finnish (FIN) AF: 0.177 AC: 9430 AN: 53184

Middle Eastern (MID) AF: 0.217 AC: 1250 AN: 5760

European-Non Finnish (NFE) AF: 0.228 AC: 253974 AN: 1111722

Other (OTH) AF: 0.211 AC: 12718 AN: 60374

GnomAD4 genome AF: 0.218 AC: 33181 AN: 152122 Hom.: 3742 Cov.: 32 AF XY: 0.211 AC XY: 15720 AN XY: 74362

African (AFR) AF: 0.272 AC: 11305 AN: 41504

American (AMR) AF: 0.144 AC: 2198 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 682 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5166

South Asian (SAS) AF: 0.194 AC: 934 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1759 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15129 AN: 67958

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.216 Hom.: 1276

Bravo AF: 0.217

TwinsUK AF: 0.223 AC: 828

ALSPAC AF: 0.231 AC: 892

ESP6500AA AF: 0.265 AC: 1169

ESP6500EA AF: 0.223 AC: 1919

ExAC AF: 0.199 AC: 24096

Asia WGS AF: 0.151 AC: 524 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.10
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.39	.;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		4.9
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.013	D;D;D
Vest4		0.30
MPC		0.24
ClinPred		0.027	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.69
Mutation Taster		=93/7	polymorphism (auto)

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: rs229526; hg19: chr22-37581422; COSMIC: COSV55396250; COSMIC: COSV55396250;