rs11779129

Variant names:

• chr8-138806660-C-A
• rs11779129
• NM_152888.3:c.1494+1108G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.1494+1108G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,016 control chromosomes in the GnomAD database, including 17,101 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 0.41 (17101 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.1494+1108G>T		intron	N/A	NP_690848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.1494+1108G>T		intron	N/A	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62534 AN: 151898 Hom.: 17052 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.412 AC: 62656 AN: 152016 Hom.: 17101 Cov.: 33 AF XY: 0.407 AC XY: 30196 AN XY: 74276

African (AFR) AF: 0.782 AC: 32420 AN: 41434

American (AMR) AF: 0.313 AC: 4775 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3472

East Asian (EAS) AF: 0.121 AC: 624 AN: 5170

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2386 AN: 10590

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18623 AN: 67936

Other (OTH) AF: 0.374 AC: 790 AN: 2112

Alfa AF: 0.316 Hom.: 34880

Bravo AF: 0.434

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11779129; hg19: chr8-139818903;