8-138860454-T-C

Variant names:

• chr8-138860454-T-C
• rs17740495
• NM_152888.3:c.659-16296A>G

Variant summary

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

The NM_152888.3(COL22A1):​c.659-16296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,232 control chromosomes in the GnomAD database, including 550 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 0.081 (550 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.659-16296A>G		intron_variant	Intron 3 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.659-16296A>G		intron_variant	Intron 3 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12370 AN: 152114 Hom.: 552 Cov.: 33

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0813 AC: 12369 AN: 152232 Hom.: 550 Cov.: 33 AF XY: 0.0794 AC XY: 5907 AN XY: 74442

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0699

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0876 Hom.: 870

Bravo AF: 0.0790

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.83

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: rs17740495; hg19: chr8-139872697;