rs6993839

Positions:

• chr8-138833277-G-A
• chr8-138833277-G-C

Variant summary

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

The NM_152888.3(COL22A1):​c.734-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 658,410 control chromosomes in the GnomAD database, including 126,761 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 0.61 (28382 hom., cov: 34)
  • Exomes 𝑓: 0.62 (98379 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL22A1	NM_152888.3	c.734-127C>T		intron_variant		ENST00000303045.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL22A1	ENST00000303045.11	c.734-127C>T		intron_variant		1	NM_152888.3	P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92525 AN: 152022 Hom.: 28350 Cov.: 34

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.621 AC: 314302 AN: 506270 Hom.: 98379 AF XY: 0.622 AC XY: 168260 AN XY: 270570

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.609 AC: 92601 AN: 152140 Hom.: 28382 Cov.: 34 AF XY: 0.612 AC XY: 45504 AN XY: 74366

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.619

Alfa AF: 0.606 Hom.: 4905

Bravo AF: 0.604

Asia WGS AF: 0.642 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6993839; hg19: chr8-139845520;