chr8-138747361-C-T

Variant names:

• chr8-138747361-C-T
• rs13255079
• NM_152888.3:c.2085+4097G>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.2085+4097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,146 control chromosomes in the GnomAD database, including 2,082 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 0.16 (2082 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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.2085+4097G>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.2085+4097G>A		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.2085+4097G>A		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.2040+4097G>A		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25070 AN: 152028 Hom.: 2084 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.165 AC: 25078 AN: 152146 Hom.: 2082 Cov.: 33 AF XY: 0.163 AC XY: 12163 AN XY: 74396

African (AFR) AF: 0.192 AC: 7977 AN: 41508

American (AMR) AF: 0.158 AC: 2420 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3468

East Asian (EAS) AF: 0.107 AC: 556 AN: 5182

South Asian (SAS) AF: 0.150 AC: 722 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1510 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10907 AN: 67976

Other (OTH) AF: 0.153 AC: 323 AN: 2116

Alfa AF: 0.144 Hom.: 877

Bravo AF: 0.168

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.55
PhyloP100		-0.33
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: rs13255079; hg19: chr8-139759604;