chr8-138794472-A-G

Variant names:

• chr8-138794472-A-G
• rs7837787
• NM_152888.3:c.1596+2347T>C

Variant summary

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

The NM_152888.3(COL22A1):​c.1596+2347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,938 control chromosomes in the GnomAD database, including 7,067 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 0.30 (7067 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1596+2347T>C		intron_variant	Intron 12 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1596+2347T>C		intron_variant	Intron 12 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44793 AN: 151822 Hom.: 7060 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.295 AC: 44837 AN: 151938 Hom.: 7067 Cov.: 32 AF XY: 0.294 AC XY: 21809 AN XY: 74264

African (AFR) AF: 0.394 AC: 16309 AN: 41430

American (AMR) AF: 0.260 AC: 3966 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3468

East Asian (EAS) AF: 0.120 AC: 621 AN: 5162

South Asian (SAS) AF: 0.361 AC: 1732 AN: 4794

European-Finnish (FIN) AF: 0.224 AC: 2360 AN: 10548

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18201 AN: 67966

Other (OTH) AF: 0.272 AC: 572 AN: 2102

Alfa AF: 0.288 Hom.: 1712

Bravo AF: 0.301

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.42
PhyloP100		-0.14
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: rs7837787; hg19: chr8-139806715;