8-138818553-C-T

Position:

• chr8-138818553-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.1245+2583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,208 control chromosomes in the GnomAD database, including 61,964 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 0.90 (61964 hom., cov: 31)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

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 (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL22A1	NM_152888.3	c.1245+2583G>A		intron_variant		ENST00000303045.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL22A1	ENST00000303045.11	c.1245+2583G>A		intron_variant		1	NM_152888.3	P1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136907 AN: 152090 Hom.: 61904 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.900 AC: 137020 AN: 152208 Hom.: 61964 Cov.: 31 AF XY: 0.898 AC XY: 66795 AN XY: 74418

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.911

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.911

Alfa AF: 0.887 Hom.: 79594

Bravo AF: 0.907

Asia WGS AF: 0.841 AC: 2925 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	0.58
DANN	Benign	0.43

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: rs1320279; hg19: chr8-139830796;