chr8-138775551-T-C

Variant names:

• chr8-138775551-T-C
• rs10092896
• NM_152888.3:c.1803+415A>G

Variant summary

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

The NM_152888.3(COL22A1):​c.1803+415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,032 control chromosomes in the GnomAD database, including 16,342 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 0.42 (16342 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1803+415A>G		intron_variant	Intron 16 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1803+415A>G		intron_variant	Intron 16 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63148 AN: 151914 Hom.: 16292 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.416 AC: 63266 AN: 152032 Hom.: 16342 Cov.: 32 AF XY: 0.411 AC XY: 30522 AN XY: 74310

African (AFR) AF: 0.734 AC: 30425 AN: 41432

American (AMR) AF: 0.355 AC: 5426 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3466

East Asian (EAS) AF: 0.121 AC: 626 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1952 AN: 4802

European-Finnish (FIN) AF: 0.236 AC: 2503 AN: 10594

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20337 AN: 67978

Other (OTH) AF: 0.382 AC: 806 AN: 2108

Alfa AF: 0.365 Hom.: 1535

Bravo AF: 0.437

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.89
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: rs10092896; hg19: chr8-139787794;