chr8-138610642-C-T

Variant names:

• chr8-138610642-C-T
• rs4341165
• NM_152888.3:c.3979-2653G>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.3979-2653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,102 control chromosomes in the GnomAD database, including 35,158 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 0.67 (35158 hom., cov: 33)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.3979-2653G>A		intron	N/A	NP_690848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.3979-2653G>A		intron	N/A	ENSP00000303153.6
	COL22A1	ENST00000341807.8	TSL:1	n.1664-2653G>A		intron	N/A
	COL22A1	ENST00000487854.1	TSL:5	n.646-2653G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101405 AN: 151984 Hom.: 35131 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.667 AC: 101480 AN: 152102 Hom.: 35158 Cov.: 33 AF XY: 0.664 AC XY: 49347 AN XY: 74342

African (AFR) AF: 0.477 AC: 19789 AN: 41466

American (AMR) AF: 0.638 AC: 9756 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2805 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3498 AN: 5166

South Asian (SAS) AF: 0.635 AC: 3059 AN: 4814

European-Finnish (FIN) AF: 0.728 AC: 7701 AN: 10582

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52549 AN: 67994

Other (OTH) AF: 0.697 AC: 1470 AN: 2110

Alfa AF: 0.741 Hom.: 67857

Bravo AF: 0.652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.47
PhyloP100		-1.9
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: rs4341165; hg19: chr8-139622885;