rs7290488

Variant names:

• chr22-37185343-C-T
• rs7290488
• NM_031910.4:c.164G>A

Variant summary

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

The NM_031910.4(C1QTNF6):​c.164G>A​(p.Gly55Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,360 control chromosomes in the GnomAD database, including 23,076 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G55S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1563 hom., cov: 31)
  • Exomes 𝑓: 0.16 (21513 hom.)
• Consequence: C1QTNF6 NM_031910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 21 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=0.0018802285).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031910.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF6	NM_031910.4	MANE Select	c.164G>A	p.Gly55Asp	missense	Exon 2 of 3	NP_114116.3
	C1QTNF6	NM_182486.2		c.164G>A	p.Gly55Asp	missense	Exon 2 of 4	NP_872292.1
	C1QTNF6	NM_001365878.1		c.107G>A	p.Gly36Asp	missense	Exon 4 of 5	NP_001352807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF6	ENST00000337843.7	TSL:1 MANE Select	c.164G>A	p.Gly55Asp	missense	Exon 2 of 3	ENSP00000338812.2
	C1QTNF6	ENST00000397110.6	TSL:1	c.164G>A	p.Gly55Asp	missense	Exon 2 of 4	ENSP00000380299.2
	C1QTNF6	ENST00000493023.1	TSL:1	n.606G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19988 AN: 152054 Hom.: 1564 Cov.: 31

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.123 AC: 30808 AN: 249906 AF XY: 0.123

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.0885

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.000273

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.164 AC: 239572 AN: 1461188 Hom.: 21513 Cov.: 32 AF XY: 0.161 AC XY: 116904 AN XY: 726914

African (AFR) AF: 0.0682 AC: 2282 AN: 33470

American (AMR) AF: 0.0928 AC: 4148 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4313 AN: 26116

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39670

South Asian (SAS) AF: 0.0506 AC: 4360 AN: 86196

European-Finnish (FIN) AF: 0.126 AC: 6693 AN: 53208

Middle Eastern (MID) AF: 0.0971 AC: 560 AN: 5768

European-Non Finnish (NFE) AF: 0.187 AC: 208025 AN: 1111706

Other (OTH) AF: 0.152 AC: 9178 AN: 60370

GnomAD4 genome AF: 0.131 AC: 19992 AN: 152172 Hom.: 1563 Cov.: 31 AF XY: 0.126 AC XY: 9361 AN XY: 74388

African (AFR) AF: 0.0787 AC: 3267 AN: 41518

American (AMR) AF: 0.127 AC: 1935 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0474 AC: 228 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12248 AN: 67972

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.157 Hom.: 4312

Bravo AF: 0.130

TwinsUK AF: 0.201 AC: 747

ALSPAC AF: 0.198 AC: 762

ESP6500AA AF: 0.0833 AC: 367

ESP6500EA AF: 0.177 AC: 1518

ExAC AF: 0.122 AC: 14785

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.3
DANN	Benign	0.95
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.33
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.044
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Vest4		0.20
MPC		0.46
ClinPred		0.0037	T
GERP RS		1.1
Varity_R		0.037
gMVP		0.46
Mutation Taster		=100/0	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: rs7290488; hg19: chr22-37581383; COSMIC: COSV107306912; COSMIC: COSV107306912;