chr8-138836664-C-T

Variant names:

• chr8-138836664-C-T
• rs9650565
• NM_152888.3:c.734-3514G>A

Variant summary

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

The NM_152888.3(COL22A1):​c.734-3514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,032 control chromosomes in the GnomAD database, including 21,941 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 0.53 (21941 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152888.3. 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
	COL22A1	NM_152888.3	MANE Select	c.734-3514G>A		intron	N/A	NP_690848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.734-3514G>A		intron	N/A	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80004 AN: 151914 Hom.: 21936 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.526 AC: 80021 AN: 152032 Hom.: 21941 Cov.: 33 AF XY: 0.530 AC XY: 39355 AN XY: 74324

African (AFR) AF: 0.364 AC: 15066 AN: 41444

American (AMR) AF: 0.600 AC: 9167 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.658 AC: 3391 AN: 5152

South Asian (SAS) AF: 0.548 AC: 2636 AN: 4814

European-Finnish (FIN) AF: 0.611 AC: 6456 AN: 10566

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39297 AN: 67980

Other (OTH) AF: 0.546 AC: 1155 AN: 2114

Alfa AF: 0.555 Hom.: 3235

Bravo AF: 0.516

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.20
PhyloP100		-1.3
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: rs9650565; hg19: chr8-139848907;