8-138731478-A-G

Variant names:

• chr8-138731478-A-G
• rs12680005
• NM_152888.3:c.2140-6038T>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.2140-6038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 151,996 control chromosomes in the GnomAD database, including 535 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 0.073 (535 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.2140-6038T>C		intron_variant	Intron 23 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.2140-6038T>C		intron_variant	Intron 23 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11141 AN: 151878 Hom.: 534 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0734 AC: 11155 AN: 151996 Hom.: 535 Cov.: 32 AF XY: 0.0779 AC XY: 5791 AN XY: 74322

African (AFR) AF: 0.0715 AC: 2967 AN: 41472

American (AMR) AF: 0.107 AC: 1640 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3464

East Asian (EAS) AF: 0.262 AC: 1341 AN: 5116

South Asian (SAS) AF: 0.0883 AC: 424 AN: 4802

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10584

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3273 AN: 67982

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0643 Hom.: 62

Bravo AF: 0.0771

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.48
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: rs12680005; hg19: chr8-139743721;