8-138752153-T-C

Variant names:

• chr8-138752153-T-C
• rs9324496
• NM_152888.3:c.2032-642A>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.2032-642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,016 control chromosomes in the GnomAD database, including 24,312 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 0.54 (24312 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.2032-642A>G		intron_variant	Intron 21 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.2032-642A>G		intron_variant	Intron 21 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82345 AN: 151898 Hom.: 24314 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.542 AC: 82363 AN: 152016 Hom.: 24312 Cov.: 32 AF XY: 0.551 AC XY: 40902 AN XY: 74298

African (AFR) AF: 0.292 AC: 12125 AN: 41478

American (AMR) AF: 0.607 AC: 9258 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2486 AN: 3462

East Asian (EAS) AF: 0.649 AC: 3343 AN: 5148

South Asian (SAS) AF: 0.696 AC: 3351 AN: 4814

European-Finnish (FIN) AF: 0.674 AC: 7118 AN: 10562

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42720 AN: 67970

Other (OTH) AF: 0.568 AC: 1202 AN: 2116

Alfa AF: 0.607 Hom.: 127489

Bravo AF: 0.525

Asia WGS AF: 0.634 AC: 2207 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	1.4
DANN	Benign	0.49
PhyloP100		-0.19
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: rs9324496; hg19: chr8-139764396;