rs4074052

Positions:

• chr8-138703583-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.2518-236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,104 control chromosomes in the GnomAD database, including 19,144 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 0.50 (19144 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

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]

COL22A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.2518-236T>C		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.2518-236T>C		intron_variant		1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000341807.8	n.263-236T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75520 AN: 151986 Hom.: 19134 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.497 AC: 75569 AN: 152104 Hom.: 19144 Cov.: 32 AF XY: 0.500 AC XY: 37147 AN XY: 74346

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.523

Alfa AF: 0.518 Hom.: 9399

Bravo AF: 0.495

Asia WGS AF: 0.610 AC: 2118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.059
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs4074052; hg19: chr8-139715826;