rs11991611

Variant names:

• chr8-138595147-G-A
• rs11991611
• NM_152888.3:c.4433-948C>T

Variant summary

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

The NM_152888.3(COL22A1):​c.4433-948C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,154 control chromosomes in the GnomAD database, including 1,125 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 0.10 (1125 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.4433-948C>T		intron_variant	Intron 62 of 64	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.4433-948C>T		intron_variant	Intron 62 of 64	1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000341807.8	n.2118-948C>T		intron_variant	Intron 36 of 38	1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15826 AN: 152034 Hom.: 1119 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0862

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

GnomAD4 genome AF: 0.104 AC: 15872 AN: 152154 Hom.: 1125 Cov.: 32 AF XY: 0.100 AC XY: 7475 AN XY: 74410

African (AFR) AF: 0.210 AC: 8699 AN: 41476

American (AMR) AF: 0.0675 AC: 1032 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5160

South Asian (SAS) AF: 0.0418 AC: 202 AN: 4830

European-Finnish (FIN) AF: 0.0550 AC: 584 AN: 10614

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0712 AC: 4843 AN: 67996

Other (OTH) AF: 0.0853 AC: 180 AN: 2110

Alfa AF: 0.0759 Hom.: 415

Bravo AF: 0.110

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.049
DANN	Benign	0.51
PhyloP100		-1.4
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: rs11991611; hg19: chr8-139607390;