rs6988229

Positions:

• chr8-138872266-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.658+5484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,082 control chromosomes in the GnomAD database, including 7,565 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 0.27 (7565 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.658+5484G>A		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.658+5484G>A		intron_variant		1	NM_152888.3	ENSP00000303153	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41631 AN: 151964 Hom.: 7552 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.274 AC: 41683 AN: 152082 Hom.: 7565 Cov.: 33 AF XY: 0.265 AC XY: 19717 AN XY: 74366

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.253

Alfa AF: 0.211 Hom.: 5360

Bravo AF: 0.288

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6988229; hg19: chr8-139884509;