8-138609125-C-T

Position:

• chr8-138609125-C-T

Variant summary

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

The ENST00000303045.11(COL22A1):​c.3979-1136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,186 control chromosomes in the GnomAD database, including 35,183 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 0.67 (35183 hom., cov: 35)
• Consequence: COL22A1 ENST00000303045.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.3979-1136G>A		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.3979-1136G>A		intron_variant		1	NM_152888.3	ENSP00000303153	P1
COL22A1	ENST00000341807.8	n.1664-1136G>A		intron_variant, non_coding_transcript_variant		1
COL22A1	ENST00000487854.1	n.646-1136G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101463 AN: 152068 Hom.: 35156 Cov.: 35

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.667 AC: 101538 AN: 152186 Hom.: 35183 Cov.: 35 AF XY: 0.664 AC XY: 49367 AN XY: 74400

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.697

Alfa AF: 0.731 Hom.: 20668

Bravo AF: 0.652

Asia WGS AF: 0.607 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.56

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: rs4076439; hg19: chr8-139621368;