8-138860377-A-G

Variant names:

• chr8-138860377-A-G
• rs1574172
• NM_152888.3:c.659-16219T>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.659-16219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,212 control chromosomes in the GnomAD database, including 53,353 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 0.83 (53353 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.659-16219T>C		intron_variant	Intron 3 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.659-16219T>C		intron_variant	Intron 3 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126955 AN: 152094 Hom.: 53321 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.835 AC: 127047 AN: 152212 Hom.: 53353 Cov.: 33 AF XY: 0.839 AC XY: 62431 AN XY: 74428

African (AFR) AF: 0.737 AC: 30587 AN: 41502

American (AMR) AF: 0.838 AC: 12821 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3023 AN: 3472

East Asian (EAS) AF: 0.972 AC: 5031 AN: 5176

South Asian (SAS) AF: 0.912 AC: 4399 AN: 4824

European-Finnish (FIN) AF: 0.920 AC: 9771 AN: 10618

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58675 AN: 68008

Other (OTH) AF: 0.815 AC: 1722 AN: 2112

Alfa AF: 0.851 Hom.: 93392

Bravo AF: 0.823

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.44
PhyloP100		-3.1
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: rs1574172; hg19: chr8-139872620;