rs12549194

Positions:

• chr8-138814594-A-C
• chr8-138814594-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.1246-1575T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,006 control chromosomes in the GnomAD database, including 6,435 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 0.29 (6435 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1246-1575T>G		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1246-1575T>G		intron_variant		1	NM_152888.3	ENSP00000303153	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43275 AN: 151890 Hom.: 6416 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.285 AC: 43327 AN: 152006 Hom.: 6435 Cov.: 32 AF XY: 0.282 AC XY: 20956 AN XY: 74294

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.265

Alfa AF: 0.282 Hom.: 1218

Bravo AF: 0.293

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs12549194; hg19: chr8-139826837;