rs4545143

Positions:

• chr8-138699486-T-A
• chr8-138699486-T-C

Variant summary

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

The NM_152888.3(COL22A1):​c.2592+626A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,262 control chromosomes in the GnomAD database, including 55,283 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 0.85 (55283 hom., cov: 35)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.2592+626A>T		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.2592+626A>T		intron_variant		1	NM_152888.3	ENSP00000303153	P1
COL22A1	ENST00000341807.8	n.337+626A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129581 AN: 152144 Hom.: 55251 Cov.: 35

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.852 AC: 129669 AN: 152262 Hom.: 55283 Cov.: 35 AF XY: 0.850 AC XY: 63251 AN XY: 74442

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.849

Alfa AF: 0.863 Hom.: 7028

Bravo AF: 0.851

Asia WGS AF: 0.790 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4545143; hg19: chr8-139711729;