8-138888935-T-C

Position:

• chr8-138888935-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.-72-5691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,166 control chromosomes in the GnomAD database, including 2,822 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 0.16 (2822 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.-72-5691A>G		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.-72-5691A>G		intron_variant		1	NM_152888.3	ENSP00000303153	P1
COL22A1	ENST00000484387.1	n.389-10619A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24302 AN: 152048 Hom.: 2819 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0389

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.160 AC: 24328 AN: 152166 Hom.: 2822 Cov.: 32 AF XY: 0.159 AC XY: 11847 AN XY: 74388

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.0829

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.121

Alfa AF: 0.105 Hom.: 1325

Bravo AF: 0.162

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.64

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: rs2318345; hg19: chr8-139901178;