rs6993839

Variant names:

• chr8-138833277-G-A
• rs6993839
• NM_152888.3:c.734-127C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-138833277-G-A
• chr8-138833277-G-C

Variant summary

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

The NM_152888.3(COL22A1):​c.734-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 658,410 control chromosomes in the GnomAD database, including 126,761 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 0.61 (28382 hom., cov: 34)
  • Exomes 𝑓: 0.62 (98379 hom.)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 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.734-127C>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.734-127C>T		intron	N/A	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.734-127C>T		intron	N/A	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.734-127C>T		intron	N/A	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92525 AN: 152022 Hom.: 28350 Cov.: 34

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.621 AC: 314302 AN: 506270 Hom.: 98379 AF XY: 0.622 AC XY: 168260 AN XY: 270570

African (AFR) AF: 0.571 AC: 8045 AN: 14094

American (AMR) AF: 0.632 AC: 17243 AN: 27262

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 10176 AN: 15660

East Asian (EAS) AF: 0.699 AC: 22114 AN: 31630

South Asian (SAS) AF: 0.629 AC: 33156 AN: 52744

European-Finnish (FIN) AF: 0.648 AC: 23587 AN: 36426

Middle Eastern (MID) AF: 0.684 AC: 2478 AN: 3624

European-Non Finnish (NFE) AF: 0.607 AC: 180221 AN: 296740

Other (OTH) AF: 0.615 AC: 17282 AN: 28090

GnomAD4 genome AF: 0.609 AC: 92601 AN: 152140 Hom.: 28382 Cov.: 34 AF XY: 0.612 AC XY: 45504 AN XY: 74366

African (AFR) AF: 0.566 AC: 23498 AN: 41486

American (AMR) AF: 0.654 AC: 9999 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2206 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3473 AN: 5170

South Asian (SAS) AF: 0.628 AC: 3027 AN: 4818

European-Finnish (FIN) AF: 0.660 AC: 6976 AN: 10576

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41316 AN: 68018

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.612 Hom.: 9671

Bravo AF: 0.604

Asia WGS AF: 0.642 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.50
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6993839; hg19: chr8-139845520;