dbSNP rs2318334: COL22A1:c.1758+458A>G (chr8-138777895-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152888.3(COL22A1):c.1758+458A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 183,712 control chromosomes in the GnomAD database, including 8,935 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 0.30 ( 7629 hom., cov: 33)

Exomes 𝑓: 0.27 ( 1306 hom. )

Consequence

COL22A1
NM_152888.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.338

Publications

5 publications found

Variant links:

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]

COL22A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3 link	c.1758+458A>G		intron_variant	Intron 15 of 64	ENST00000303045.11	NP_690848.1	Q8NFW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11 link	c.1758+458A>G		intron_variant	Intron 15 of 64	1	NM_152888.3	ENSP00000303153.6		Q8NFW1-1
COL22A1	ENST00000522546.1 link	c.*368A>G		downstream_gene_variant		3		ENSP00000428244.1		H0YAX7

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

45995

AN:

151954

Hom.:

7616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.268

AC:

8483

AN:

31640

Hom.:

1306

Cov.:

AF XY:

0.273

AC XY:

4532

AN XY:

16580

show subpopulations

African (AFR)

AF:

0.428

AC:

142

AN:

332

American (AMR)

AF:

0.293

AC:

931

AN:

3180

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

140

AN:

674

East Asian (EAS)

AF:

0.111

AC:

AN:

630

South Asian (SAS)

AF:

0.359

AC:

1726

AN:

4812

European-Finnish (FIN)

AF:

0.192

AC:

217

AN:

1130

Middle Eastern (MID)

AF:

0.342

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.251

AC:

4800

AN:

19160

Other (OTH)

AF:

0.260

AC:

416

AN:

1602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

285

569

854

1138

1423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.303

AC:

46042

AN:

152072

Hom.:

7629

Cov.:

AF XY:

0.301

AC XY:

22353

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.427

AC:

17705

AN:

41438

American (AMR)

AF:

0.265

AC:

4053

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

775

AN:

3464

East Asian (EAS)

AF:

0.122

AC:

633

AN:

5172

South Asian (SAS)

AF:

0.360

AC:

1737

AN:

4824

European-Finnish (FIN)

AF:

0.216

AC:

2284

AN:

10598

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17963

AN:

67978

Other (OTH)

AF:

0.275

AC:

581

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1583

3167

4750

6334

7917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.285

Hom.:

4261

Bravo

AF:

0.312

Asia WGS

AF:

0.247

AC:

857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.3

(source)

DANN

Benign

0.30

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over