8-138860454-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000303045.11(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 ENST00000303045.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303045.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.659-16296A>G		intron	N/A	NP_690848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.659-16296A>G		intron	N/A	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

African (AFR) AF: 0.0850 AC: 3530 AN: 41528

American (AMR) AF: 0.0695 AC: 1062 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4828

European-Finnish (FIN) AF: 0.0699 AC: 742 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0925 AC: 6290 AN: 68008

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0865 Hom.: 1357

Bravo AF: 0.0790

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.83
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17740495; hg19: chr8-139872697;