NM_152888.3:c.2517+1577G>C

Variant names:

• chr8-138714105-C-G
• rs4282617
• NM_152888.3:c.2517+1577G>C

Variant summary

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

The NM_152888.3(COL22A1):​c.2517+1577G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,082 control chromosomes in the GnomAD database, including 41,151 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 0.73 (41151 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 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.2517+1577G>C		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.2517+1577G>C		intron	N/A	ENSP00000303153.6
	COL22A1	ENST00000341807.8	TSL:1	n.262+1577G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111428 AN: 151964 Hom.: 41122 Cov.: 32

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.733 AC: 111508 AN: 152082 Hom.: 41151 Cov.: 32 AF XY: 0.732 AC XY: 54443 AN XY: 74338

African (AFR) AF: 0.660 AC: 27374 AN: 41470

American (AMR) AF: 0.762 AC: 11648 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4201 AN: 5144

South Asian (SAS) AF: 0.782 AC: 3770 AN: 4820

European-Finnish (FIN) AF: 0.689 AC: 7284 AN: 10566

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.766 AC: 52081 AN: 68012

Other (OTH) AF: 0.741 AC: 1561 AN: 2106

Alfa AF: 0.689 Hom.: 2345

Bravo AF: 0.733

Asia WGS AF: 0.767 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.50
PhyloP100		-0.12
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: rs4282617; hg19: chr8-139726348;