chr8-138759268-T-C

Variant names:

• chr8-138759268-T-C
• rs2873682
• NM_152888.3:c.1902+975A>G

Variant summary

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

The NM_152888.3(COL22A1):​c.1902+975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,050 control chromosomes in the GnomAD database, including 34,015 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 0.66 (34015 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1902+975A>G		intron_variant	Intron 18 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1902+975A>G		intron_variant	Intron 18 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100725 AN: 151932 Hom.: 34001 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.663 AC: 100773 AN: 152050 Hom.: 34015 Cov.: 32 AF XY: 0.670 AC XY: 49768 AN XY: 74316

African (AFR) AF: 0.554 AC: 22984 AN: 41456

American (AMR) AF: 0.764 AC: 11676 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3468

East Asian (EAS) AF: 0.927 AC: 4792 AN: 5168

South Asian (SAS) AF: 0.738 AC: 3558 AN: 4822

European-Finnish (FIN) AF: 0.695 AC: 7354 AN: 10574

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45675 AN: 67952

Other (OTH) AF: 0.691 AC: 1461 AN: 2114

Alfa AF: 0.672 Hom.: 18017

Bravo AF: 0.663

Asia WGS AF: 0.805 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.63
PhyloP100		0.12
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: rs2873682; hg19: chr8-139771511;