rs6991720

Positions:

• chr8-138790270-C-G

Variant summary

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

The NM_152888.3(COL22A1):​c.1596+6549G>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 152,036 control chromosomes in the GnomAD database, including 7,072 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 (7072 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1596+6549G>C		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1596+6549G>C		intron_variant		1	NM_152888.3	ENSP00000303153	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44800 AN: 151916 Hom.: 7063 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.295 AC: 44847 AN: 152036 Hom.: 7072 Cov.: 32 AF XY: 0.293 AC XY: 21809 AN XY: 74312

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.273

Alfa AF: 0.282 Hom.: 692

Bravo AF: 0.301

Asia WGS AF: 0.245 AC: 852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs6991720; hg19: chr8-139802513;