8-138847070-G-A

Position:

• chr8-138847070-G-A

Variant summary

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

The NM_152888.3(COL22A1):​c.659-2912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,030 control chromosomes in the GnomAD database, including 21,106 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 0.50 (21106 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL22A1	NM_152888.3	c.659-2912C>T		intron_variant		ENST00000303045.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL22A1	ENST00000303045.11	c.659-2912C>T		intron_variant		1	NM_152888.3	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76373 AN: 151912 Hom.: 21107 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.502 AC: 76393 AN: 152030 Hom.: 21106 Cov.: 32 AF XY: 0.504 AC XY: 37441 AN XY: 74298

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.514

Alfa AF: 0.587 Hom.: 36304

Bravo AF: 0.480

Asia WGS AF: 0.644 AC: 2236 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	0.027
DANN	Benign	0.29

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: rs2318331; hg19: chr8-139859313;