rs4909439

Variant names:

• chr8-138646504-C-A
• rs4909439
• NM_152888.3:c.3501+125G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-138646504-C-A
• chr8-138646504-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152888.3(COL22A1):​c.3501+125G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 516,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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>T		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>T		intron	N/A	ENSP00000303153.6
	COL22A1	ENST00000341807.8	TSL:1	n.1186+125G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000194 AC: 1 AN: 516046 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 262600

African (AFR) AF: 0.00 AC: 0 AN: 12668

American (AMR) AF: 0.00 AC: 0 AN: 12584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13248

East Asian (EAS) AF: 0.00 AC: 0 AN: 27386

South Asian (SAS) AF: 0.0000337 AC: 1 AN: 29660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 354608

Other (OTH) AF: 0.00 AC: 0 AN: 27404

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0070
DANN	Benign	0.29
PhyloP100		-3.8

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;