rs9650566

Variant names:

• chr8-138842447-G-A
• rs9650566
• NM_152888.3:c.733+1637C>T

Variant summary

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

The NM_152888.3(COL22A1):​c.733+1637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,110 control chromosomes in the GnomAD database, including 15,253 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 0.41 (15253 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• Publications: 4 publications found

Genes affected

COL22A1 (HGNC:22989): (collagen type XXII alpha 1 chain) This gene encodes member of the collagen family which is thought to contribute to the stabilization of myotendinous junctions and strengthen skeletal muscle attachments during contractile activity. It belongs to the fibril-associated collagens with interrupted triple helix (FACIT) subset of the collagen superfamily, which associate with collagen fibers through their C-terminal collagenous domains and mediate protein-protein interactions through their N-terminal noncollagenous domains. The encoded protein is deposited in the basement membrane zone of the myotendinous junction which is present only at the tissue junctions of muscles, tendons, the heart, articular cartilage, and skin. A knockdown of the orthologous zebrafish gene induces a muscular dystrophy by disruption of the myotendinous junction. [provided by RefSeq, May 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.733+1637C>T		intron_variant	Intron 4 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.733+1637C>T		intron_variant	Intron 4 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61703 AN: 151992 Hom.: 15254 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.406 AC: 61691 AN: 152110 Hom.: 15253 Cov.: 33 AF XY: 0.409 AC XY: 30390 AN XY: 74324

African (AFR) AF: 0.109 AC: 4543 AN: 41534

American (AMR) AF: 0.514 AC: 7856 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2359 AN: 5174

South Asian (SAS) AF: 0.463 AC: 2226 AN: 4806

European-Finnish (FIN) AF: 0.528 AC: 5575 AN: 10556

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35801 AN: 67974

Other (OTH) AF: 0.429 AC: 905 AN: 2108

Alfa AF: 0.479 Hom.: 7272

Bravo AF: 0.388

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		0.30
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: rs9650566; hg19: chr8-139854690;