8-138646504-C-T

Position:

• chr8-138646504-C-T

Variant summary

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

The NM_152888.3(COL22A1):​c.3501+125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 667,384 control chromosomes in the GnomAD database, including 238,659 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 0.82 (51152 hom., cov: 31)
  • Exomes 𝑓: 0.85 (187507 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85

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]

COL22A1 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.3501+125G>A		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.3501+125G>A		intron_variant		1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000341807.8	n.1186+125G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124160 AN: 151962 Hom.: 51121 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.847

GnomAD4 exome AF: 0.851 AC: 438700 AN: 515304 Hom.: 187507 AF XY: 0.848 AC XY: 222400 AN XY: 262214

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.924

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.725

Gnomad4 FIN exome AF: 0.867

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.849

GnomAD4 genome AF: 0.817 AC: 124245 AN: 152080 Hom.: 51152 Cov.: 31 AF XY: 0.817 AC XY: 60744 AN XY: 74320

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.848

Alfa AF: 0.851 Hom.: 75781

Bravo AF: 0.814

Asia WGS AF: 0.779 AC: 2711 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	0.0080
DANN	Benign	0.17

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: rs4909439; hg19: chr8-139658747; COSMIC: COSV57342961;