8-138651374-A-G

Variant names:

• chr8-138651374-A-G
• rs3923549
• NM_152888.3:c.3334-1596T>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.3334-1596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,154 control chromosomes in the GnomAD database, including 55,148 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 0.85 (55148 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.3334-1596T>C		intron_variant	Intron 45 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.3334-1596T>C		intron_variant	Intron 45 of 64	1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000341807.8	n.1019-1596T>C		intron_variant	Intron 19 of 38	1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128605 AN: 152034 Hom.: 55102 Cov.: 33

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.846 AC: 128707 AN: 152154 Hom.: 55148 Cov.: 33 AF XY: 0.847 AC XY: 62988 AN XY: 74376

African (AFR) AF: 0.693 AC: 28748 AN: 41476

American (AMR) AF: 0.858 AC: 13131 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3470

East Asian (EAS) AF: 0.927 AC: 4783 AN: 5160

South Asian (SAS) AF: 0.822 AC: 3959 AN: 4814

European-Finnish (FIN) AF: 0.900 AC: 9537 AN: 10602

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62340 AN: 68014

Other (OTH) AF: 0.868 AC: 1835 AN: 2114

Alfa AF: 0.887 Hom.: 31436

Bravo AF: 0.840

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		0.11
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: rs3923549; hg19: chr8-139663617;