rs7014497

Variant names:

• chr8-138842032-C-T
• rs7014497
• NM_152888.3:c.733+2052G>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.733+2052G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,996 control chromosomes in the GnomAD database, including 20,893 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 (20893 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 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.733+2052G>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.733+2052G>A		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.733+2052G>A		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.733+2052G>A		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76086 AN: 151878 Hom.: 20895 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.501 AC: 76099 AN: 151996 Hom.: 20893 Cov.: 33 AF XY: 0.502 AC XY: 37299 AN XY: 74286

African (AFR) AF: 0.263 AC: 10896 AN: 41462

American (AMR) AF: 0.584 AC: 8913 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2066 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2323 AN: 5154

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4820

European-Finnish (FIN) AF: 0.580 AC: 6122 AN: 10554

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41301 AN: 67952

Other (OTH) AF: 0.542 AC: 1144 AN: 2112

Alfa AF: 0.556 Hom.: 17221

Bravo AF: 0.489

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.31
PhyloP100		-2.9
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: rs7014497; hg19: chr8-139854275;