8-138646504-C-T

Variant names:

• chr8-138646504-C-T
• rs4909439
• NM_152888.3:c.3501+125G>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.3501+125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 667,384 control chromosomes in the GnomAD database, including 238,659 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 0.82 (51152 hom., cov: 31)
  • Exomes 𝑓: 0.85 (187507 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.3501+125G>A		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.3501+125G>A		intron	N/A	ENSP00000303153.6
	COL22A1	ENST00000341807.8	TSL:1	n.1186+125G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124160 AN: 151962 Hom.: 51121 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.847

GnomAD4 exome AF: 0.851 AC: 438700 AN: 515304 Hom.: 187507 AF XY: 0.848 AC XY: 222400 AN XY: 262214

African (AFR) AF: 0.721 AC: 9113 AN: 12644

American (AMR) AF: 0.783 AC: 9841 AN: 12566

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 12226 AN: 13234

East Asian (EAS) AF: 0.849 AC: 23233 AN: 27364

South Asian (SAS) AF: 0.725 AC: 21458 AN: 29596

European-Finnish (FIN) AF: 0.867 AC: 30337 AN: 34974

Middle Eastern (MID) AF: 0.876 AC: 3049 AN: 3482

European-Non Finnish (NFE) AF: 0.865 AC: 306195 AN: 354072

Other (OTH) AF: 0.849 AC: 23248 AN: 27372

GnomAD4 genome AF: 0.817 AC: 124245 AN: 152080 Hom.: 51152 Cov.: 31 AF XY: 0.817 AC XY: 60744 AN XY: 74320

African (AFR) AF: 0.719 AC: 29799 AN: 41462

American (AMR) AF: 0.825 AC: 12602 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3220 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4595 AN: 5154

South Asian (SAS) AF: 0.712 AC: 3427 AN: 4814

European-Finnish (FIN) AF: 0.863 AC: 9117 AN: 10568

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58649 AN: 68012

Other (OTH) AF: 0.848 AC: 1789 AN: 2110

Alfa AF: 0.848 Hom.: 94082

Bravo AF: 0.814

Asia WGS AF: 0.779 AC: 2711 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	0.0080
DANN	Benign	0.17
PhyloP100		-3.8
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: rs4909439; hg19: chr8-139658747; COSMIC: COSV57342961;