rs2318334

Variant names:

• chr8-138777895-T-C
• rs2318334
• NM_152888.3:c.1758+458A>G

Variant summary

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

The NM_152888.3(COL22A1):​c.1758+458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 183,712 control chromosomes in the GnomAD database, including 8,935 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 0.30 (7629 hom., cov: 33)
  • Exomes 𝑓: 0.27 (1306 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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.1758+458A>G		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.1758+458A>G		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.1758+458A>G		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.1713+458A>G		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45995 AN: 151954 Hom.: 7616 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.268 AC: 8483 AN: 31640 Hom.: 1306 Cov.: 0 AF XY: 0.273 AC XY: 4532 AN XY: 16580

African (AFR) AF: 0.428 AC: 142 AN: 332

American (AMR) AF: 0.293 AC: 931 AN: 3180

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 140 AN: 674

East Asian (EAS) AF: 0.111 AC: 70 AN: 630

South Asian (SAS) AF: 0.359 AC: 1726 AN: 4812

European-Finnish (FIN) AF: 0.192 AC: 217 AN: 1130

Middle Eastern (MID) AF: 0.342 AC: 41 AN: 120

European-Non Finnish (NFE) AF: 0.251 AC: 4800 AN: 19160

Other (OTH) AF: 0.260 AC: 416 AN: 1602

GnomAD4 genome AF: 0.303 AC: 46042 AN: 152072 Hom.: 7629 Cov.: 33 AF XY: 0.301 AC XY: 22353 AN XY: 74346

African (AFR) AF: 0.427 AC: 17705 AN: 41438

American (AMR) AF: 0.265 AC: 4053 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 775 AN: 3464

East Asian (EAS) AF: 0.122 AC: 633 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1737 AN: 4824

European-Finnish (FIN) AF: 0.216 AC: 2284 AN: 10598

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17963 AN: 67978

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.285 Hom.: 4261

Bravo AF: 0.312

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.30
PhyloP100		-0.34
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: rs2318334; hg19: chr8-139790138;