Variant chr8-138724690-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000303045.11(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
ENST00000303045.11 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.429

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3 linkuse as main transcript	c.2194-22G>T		intron_variant		ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11 linkuse as main transcript	c.2194-22G>T		intron_variant		1	NM_152888.3	ENSP00000303153	P1	Q8NFW1-1

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77482

AN:

152080

Hom.:

19936

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.486

AC:

121548

AN:

250292

Hom.:

30235

AF XY:

0.484

AC XY:

65518

AN XY:

135378

show subpopulations

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 SAS exome

AF:

0.426

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.:

AF XY:

0.503

AC XY:

364203

AN XY:

724484

show subpopulations

Gnomad4 AFR exome

AF:

0.522

Gnomad4 AMR exome

AF:

0.473

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.429

Gnomad4 FIN exome

AF:

0.572

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

AF:

0.510

AC:

77557

AN:

152198

Hom.:

19961

Cov.:

AF XY:

0.508

AC XY:

37785

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.528

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.512

Hom.:

12883

Bravo

AF:

0.501

Asia WGS

AF:

0.381

AC:

1326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.061

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over