22-37193765-C-T

Variant names:

• chr22-37193765-C-T
• rs5756546
• NM_001365878.1:c.-70-2837G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001365878.1(C1QTNF6):​c.-70-2837G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,078 control chromosomes in the GnomAD database, including 2,686 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.

• Frequency: Genomes: 𝑓 0.18 (2686 hom., cov: 33)
• Consequence: C1QTNF6 NM_001365878.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF6	NM_001365878.1	c.-70-2837G>A		intron_variant	Intron 2 of 4		NP_001352807.1
C1QTNF6	XM_024452150.2	c.-190+1616G>A		intron_variant	Intron 2 of 5		XP_024307918.1
C1QTNF6	XM_024452153.2	c.-190+1616G>A		intron_variant	Intron 2 of 5		XP_024307921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF6	ENST00000467564.5	n.224+1616G>A		intron_variant	Intron 2 of 4	3
C1QTNF6	ENST00000470655.5	n.2921+1616G>A		intron_variant	Intron 1 of 8	2
C1QTNF6	ENST00000497071.1	n.433+1616G>A		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27448 AN: 151958 Hom.: 2689 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27432 AN: 152078 Hom.: 2686 Cov.: 33 AF XY: 0.176 AC XY: 13116 AN XY: 74354

African (AFR) AF: 0.122 AC: 5068 AN: 41472

American (AMR) AF: 0.133 AC: 2039 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3472

East Asian (EAS) AF: 0.103 AC: 531 AN: 5172

South Asian (SAS) AF: 0.183 AC: 883 AN: 4818

European-Finnish (FIN) AF: 0.198 AC: 2092 AN: 10558

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15571 AN: 67970

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.204 Hom.: 5539

Bravo AF: 0.170

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.42
DANN	Benign	0.74
PhyloP100		-0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5756546; hg19: chr22-37589805;