8-138818553-C-T

Variant names:

• chr8-138818553-C-T
• rs1320279
• NM_152888.3:c.1245+2583G>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.1245+2583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,208 control chromosomes in the GnomAD database, including 61,964 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 0.90 (61964 hom., cov: 31)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1245+2583G>A		intron_variant	Intron 7 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1245+2583G>A		intron_variant	Intron 7 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136907 AN: 152090 Hom.: 61904 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.900 AC: 137020 AN: 152208 Hom.: 61964 Cov.: 31 AF XY: 0.898 AC XY: 66795 AN XY: 74418

African (AFR) AF: 0.977 AC: 40609 AN: 41552

American (AMR) AF: 0.900 AC: 13760 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3164 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3777 AN: 5154

South Asian (SAS) AF: 0.927 AC: 4465 AN: 4818

European-Finnish (FIN) AF: 0.832 AC: 8814 AN: 10594

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59407 AN: 68008

Other (OTH) AF: 0.911 AC: 1925 AN: 2114

Alfa AF: 0.893 Hom.: 127064

Bravo AF: 0.907

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.43
PhyloP100		-0.46
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: rs1320279; hg19: chr8-139830796;