rs229527

Variant names:

• chr22-37185445-C-A
• rs229527
• NM_031910.4:c.62G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37185445-C-A
• chr22-37185445-C-G
• chr22-37185445-C-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.62G>T​(p.Gly21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,599,432 control chromosomes in the GnomAD database, including 147,086 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (12907 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134179 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 84 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=6.8937634E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF6	NM_031910.4	c.62G>T	p.Gly21Val	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.62G>T	p.Gly21Val	missense_variant	Exon 2 of 3	1	NM_031910.4	ENSP00000338812.2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61739 AN: 151776 Hom.: 12908 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.432 AC: 103902 AN: 240514 AF XY: 0.437

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.661

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.428 AC: 619783 AN: 1447538 Hom.: 134179 Cov.: 43 AF XY: 0.430 AC XY: 308798 AN XY: 718952

African (AFR) AF: 0.344 AC: 11336 AN: 32988

American (AMR) AF: 0.375 AC: 16271 AN: 43400

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12431 AN: 25542

East Asian (EAS) AF: 0.662 AC: 25986 AN: 39260

South Asian (SAS) AF: 0.456 AC: 38748 AN: 85016

European-Finnish (FIN) AF: 0.392 AC: 20388 AN: 52024

Middle Eastern (MID) AF: 0.502 AC: 2872 AN: 5720

European-Non Finnish (NFE) AF: 0.422 AC: 465348 AN: 1103840

Other (OTH) AF: 0.442 AC: 26403 AN: 59748

GnomAD4 genome AF: 0.407 AC: 61758 AN: 151894 Hom.: 12907 Cov.: 32 AF XY: 0.408 AC XY: 30256 AN XY: 74228

African (AFR) AF: 0.344 AC: 14236 AN: 41408

American (AMR) AF: 0.405 AC: 6188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1751 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3364 AN: 5158

South Asian (SAS) AF: 0.455 AC: 2191 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4025 AN: 10560

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28568 AN: 67890

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.420 Hom.: 57986

Bravo AF: 0.408

TwinsUK AF: 0.428 AC: 1587

ALSPAC AF: 0.422 AC: 1626

ESP6500AA AF: 0.344 AC: 1517

ESP6500EA AF: 0.423 AC: 3638

ExAC AF: 0.431 AC: 52364

Asia WGS AF: 0.521 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.49	.;T;T
MetaRNN	Benign	0.0000069	T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		0.79
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;D
REVEL	Benign	0.057
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.29	T;T;T
Vest4		0.14
MPC		0.71
ClinPred		0.016	T
GERP RS		1.0
Varity_R		0.024
gMVP		0.46
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs229527; hg19: chr22-37581485; COSMIC: COSV107306900; COSMIC: COSV107306900;