rs10112806

Variant names:

• chr8-138724690-C-A
• rs10112806
• NM_152888.3:c.2194-22G>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.2194-22G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,607,724 control chromosomes in the GnomAD database, including 208,529 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 (19961 hom., cov: 35)
  • Exomes 𝑓: 0.51 (188568 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 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.2194-22G>T		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.2194-22G>T		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.2194-22G>T		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.2149-22G>T		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77482 AN: 152080 Hom.: 19936 Cov.: 35

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.493

GnomAD2 exomes AF: 0.486 AC: 121548 AN: 250292 AF XY: 0.484

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.437

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.490

GnomAD4 exome AF: 0.505 AC: 735130 AN: 1455526 Hom.: 188568 Cov.: 32 AF XY: 0.503 AC XY: 364203 AN XY: 724484

African (AFR) AF: 0.522 AC: 17398 AN: 33326

American (AMR) AF: 0.473 AC: 21138 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11538 AN: 26098

East Asian (EAS) AF: 0.281 AC: 11151 AN: 39676

South Asian (SAS) AF: 0.429 AC: 36930 AN: 86138

European-Finnish (FIN) AF: 0.572 AC: 30514 AN: 53338

Middle Eastern (MID) AF: 0.449 AC: 2589 AN: 5762

European-Non Finnish (NFE) AF: 0.519 AC: 574238 AN: 1106322

Other (OTH) AF: 0.492 AC: 29634 AN: 60178

GnomAD4 genome AF: 0.510 AC: 77557 AN: 152198 Hom.: 19961 Cov.: 35 AF XY: 0.508 AC XY: 37785 AN XY: 74418

African (AFR) AF: 0.522 AC: 21678 AN: 41520

American (AMR) AF: 0.475 AC: 7265 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1399 AN: 5166

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4824

European-Finnish (FIN) AF: 0.570 AC: 6037 AN: 10592

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35874 AN: 67996

Other (OTH) AF: 0.491 AC: 1038 AN: 2116

Alfa AF: 0.508 Hom.: 17021

Bravo AF: 0.501

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.061
DANN	Benign	0.42
PhyloP100		-0.43
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10112806;

hg19: chr8-139736933;

COSMIC: COSV57323973;

COSMIC: COSV57323973;