rs4075073

Variant names:

• chr8-138726718-G-T
• rs4075073
• NM_152888.3:c.2140-1278C>A

Variant summary

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

The NM_152888.3(COL22A1):​c.2140-1278C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,434 control chromosomes in the GnomAD database, including 12,501 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 0.40 (12501 hom., cov: 31)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.2140-1278C>A		intron_variant	Intron 23 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.2140-1278C>A		intron_variant	Intron 23 of 64	1	NM_152888.3	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60713 AN: 151310 Hom.: 12470 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.401 AC: 60791 AN: 151434 Hom.: 12501 Cov.: 31 AF XY: 0.399 AC XY: 29530 AN XY: 73994

African (AFR) AF: 0.515 AC: 21219 AN: 41200

American (AMR) AF: 0.393 AC: 5985 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1073 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1938 AN: 5124

South Asian (SAS) AF: 0.355 AC: 1703 AN: 4796

European-Finnish (FIN) AF: 0.341 AC: 3587 AN: 10504

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23915 AN: 67814

Other (OTH) AF: 0.395 AC: 833 AN: 2110

Alfa AF: 0.369 Hom.: 37699

Bravo AF: 0.415

Asia WGS AF: 0.384 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		-0.25
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: rs4075073; hg19: chr8-139738961;