8-138808599-G-C

Variant names:

• chr8-138808599-G-C
• rs16893541
• NM_152888.3:c.1450-787C>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.1450-787C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,986 control chromosomes in the GnomAD database, including 7,879 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 0.31 (7879 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1450-787C>G		intron_variant	Intron 9 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1450-787C>G		intron_variant	Intron 9 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47337 AN: 151868 Hom.: 7859 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.312 AC: 47397 AN: 151986 Hom.: 7879 Cov.: 33 AF XY: 0.309 AC XY: 22936 AN XY: 74286

African (AFR) AF: 0.418 AC: 17303 AN: 41412

American (AMR) AF: 0.278 AC: 4237 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3468

East Asian (EAS) AF: 0.121 AC: 627 AN: 5176

South Asian (SAS) AF: 0.367 AC: 1767 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2454 AN: 10548

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19258 AN: 67988

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.144 Hom.: 226

Bravo AF: 0.318

Asia WGS AF: 0.253 AC: 879 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.34
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs16893541; hg19: chr8-139820842;