rs6986041

Variant names:

• chr8-138907024-C-T
• rs6986041
• NM_152888.3:c.-73+6595G>A

Variant summary

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

The NM_152888.3(COL22A1):​c.-73+6595G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,096 control chromosomes in the GnomAD database, including 26,127 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 0.58 (26127 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.-73+6595G>A		intron	N/A	NP_690848.1	Q8NFW1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.-73+6595G>A		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.-73+6595G>A		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.-73+6595G>A		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88447 AN: 151978 Hom.: 26102 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.582 AC: 88513 AN: 152096 Hom.: 26127 Cov.: 33 AF XY: 0.575 AC XY: 42764 AN XY: 74342

African (AFR) AF: 0.496 AC: 20542 AN: 41454

American (AMR) AF: 0.574 AC: 8780 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2242 AN: 3466

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5176

South Asian (SAS) AF: 0.488 AC: 2353 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5911 AN: 10582

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44039 AN: 67984

Other (OTH) AF: 0.618 AC: 1306 AN: 2114

Alfa AF: 0.631 Hom.: 91621

Bravo AF: 0.582

Asia WGS AF: 0.552 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		-0.15
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: rs6986041; hg19: chr8-139919267;