rs4073446

Positions:

• chr8-138653631-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.3333+2266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,106 control chromosomes in the GnomAD database, including 47,916 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 0.77 (47916 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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

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 = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL22A1	NM_152888.3	c.3333+2266T>C		intron_variant		ENST00000303045.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL22A1	ENST00000303045.11	c.3333+2266T>C		intron_variant		1	NM_152888.3	P1
COL22A1	ENST00000341807.8	n.1018+2266T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116498 AN: 151988 Hom.: 47903 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.766 AC: 116546 AN: 152106 Hom.: 47916 Cov.: 32 AF XY: 0.770 AC XY: 57223 AN XY: 74356

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.899

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.788

Alfa AF: 0.877 Hom.: 81104

Bravo AF: 0.746

Asia WGS AF: 0.810 AC: 2818 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	2.7
DANN	Benign	0.66

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: rs4073446; hg19: chr8-139665874;