rs863223441

chr9-134738455-CCT-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_000093.5(COL5A1):c.1390-12_1390-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,614,008 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: COL5A1 NM_000093.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.226

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 9-134738455-CCT-C is Benign according to our data. Variant chr9-134738455-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 212931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134738455-CCT-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 197 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.1390-12_1390-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.1390-12_1390-11del		splice_polypyrimidine_tract_variant, intron_variant
COL5A1	XM_017014266.3	c.1390-12_1390-11del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.1390-12_1390-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.1390-12_1390-11del		splice_polypyrimidine_tract_variant, intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 197 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00781

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00136 AC: 341 AN: 251128 Hom.: 0 AF XY: 0.00127 AC XY: 172 AN XY: 135802

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00788

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00121 AC: 1773 AN: 1461682 Hom.: 6 AF XY: 0.00110 AC XY: 800 AN XY: 727160

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00780

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.000927

GnomAD4 genome AF: 0.00129 AC: 197 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74472

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00781

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.000733

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant was found in TAAD -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Oct 29, 2023	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Ehlers-Danlos syndrome, classic type, 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863223441; hg19: chr9-137630301;