8-138766637-C-T

Variant names:

• chr8-138766637-C-T
• rs11166844
• NM_152888.3:c.1804-4171G>A

Variant summary

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

The NM_152888.3(COL22A1):​c.1804-4171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,898 control chromosomes in the GnomAD database, including 22,598 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 0.51 (22598 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.1804-4171G>A		intron	N/A	NP_690848.1	Q8NFW1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.1804-4171G>A		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.1804-4171G>A		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.1759-4171G>A		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77425 AN: 151780 Hom.: 22583 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.510 AC: 77456 AN: 151898 Hom.: 22598 Cov.: 32 AF XY: 0.519 AC XY: 38513 AN XY: 74270

African (AFR) AF: 0.212 AC: 8766 AN: 41426

American (AMR) AF: 0.663 AC: 10127 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2220 AN: 3464

East Asian (EAS) AF: 0.841 AC: 4324 AN: 5140

South Asian (SAS) AF: 0.674 AC: 3241 AN: 4812

European-Finnish (FIN) AF: 0.600 AC: 6328 AN: 10548

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40552 AN: 67922

Other (OTH) AF: 0.549 AC: 1159 AN: 2112

Alfa AF: 0.572 Hom.: 70185

Bravo AF: 0.502

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.55
PhyloP100		-1.2
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: rs11166844; hg19: chr8-139778880;