rs6988229

Variant names:

• chr8-138872266-C-T
• rs6988229
• NM_152888.3:c.658+5484G>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.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
• Publications: 14 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=-0.85).
• 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 rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.658+5484G>A		intron_variant	Intron 3 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.658+5484G>A		intron_variant	Intron 3 of 64	1	NM_152888.3	ENSP00000303153.6

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

African (AFR) AF: 0.514 AC: 21306 AN: 41438

American (AMR) AF: 0.194 AC: 2974 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5184

South Asian (SAS) AF: 0.104 AC: 504 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10592

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13729 AN: 67964

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.225 Hom.: 15044

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
PhyloP100		-0.72
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: rs6988229; hg19: chr8-139884509;