8-138784739-C-T

Variant names:

• chr8-138784739-C-T
• rs1574370
• NM_152888.3:c.1597-3759G>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.1597-3759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,980 control chromosomes in the GnomAD database, including 11,234 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 0.35 (11234 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.1597-3759G>A		intron_variant	Intron 12 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.1597-3759G>A		intron_variant	Intron 12 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53075 AN: 151862 Hom.: 11216 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.350 AC: 53151 AN: 151980 Hom.: 11234 Cov.: 32 AF XY: 0.347 AC XY: 25811 AN XY: 74298

African (AFR) AF: 0.595 AC: 24670 AN: 41432

American (AMR) AF: 0.276 AC: 4211 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.121 AC: 623 AN: 5170

South Asian (SAS) AF: 0.398 AC: 1911 AN: 4804

European-Finnish (FIN) AF: 0.216 AC: 2288 AN: 10574

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17722 AN: 67940

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.320 Hom.: 1487

Bravo AF: 0.363

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.53
PhyloP100		-0.77
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: rs1574370; hg19: chr8-139796982;