rs16893545

Variant names:

• chr8-138866718-A-C
• rs16893545
• NM_152888.3:c.658+11032T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-138866718-A-C
• chr8-138866718-A-G
• chr8-138866718-A-T

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+11032T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,210 control chromosomes in the GnomAD database, including 5,024 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 0.22 (5024 hom., cov: 34)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.658+11032T>G		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+11032T>G		intron_variant	Intron 3 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33597 AN: 152092 Hom.: 5010 Cov.: 34

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.221 AC: 33654 AN: 152210 Hom.: 5024 Cov.: 34 AF XY: 0.213 AC XY: 15828 AN XY: 74428

African (AFR) AF: 0.423 AC: 17568 AN: 41502

American (AMR) AF: 0.180 AC: 2747 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5184

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1358 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10977 AN: 68004

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.173 Hom.: 1861

Bravo AF: 0.234

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.46
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: rs16893545; hg19: chr8-139878961;