rs141152269

chr9-134818983-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000093.5(COL5A1):c.4393-17C>T 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 0.00257 in 1,613,386 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (13 hom.)
• Consequence: COL5A1 NM_000093.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.720

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-134818983-C-T is Benign according to our data. Variant chr9-134818983-C-T is described in ClinVar as [Benign]. Clinvar id is 136896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (750/152296) while in subpopulation AFR AF= 0.00977 (406/41568). AF 95% confidence interval is 0.00898. There are 3 homozygotes in gnomad4. There are 356 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.4393-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371817.8
COL5A1	NM_001278074.1	c.4393-17C>T		splice_polypyrimidine_tract_variant, intron_variant
COL5A1	XM_017014266.3	c.4393-17C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.4393-17C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.4393-17C>T		splice_polypyrimidine_tract_variant, intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.00492 AC: 748 AN: 152178 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00276 AC: 694 AN: 251168 Hom.: 6 AF XY: 0.00264 AC XY: 359 AN XY: 135802

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00233 AC: 3398 AN: 1461090 Hom.: 13 Cov.: 33 AF XY: 0.00219 AC XY: 1594 AN XY: 726854

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00432

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0000379

Gnomad4 NFE exome AF: 0.00213

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00492 AC: 750 AN: 152296 Hom.: 3 Cov.: 32 AF XY: 0.00478 AC XY: 356 AN XY: 74462

Gnomad4 AFR AF: 0.00977

Gnomad4 AMR AF: 0.00974

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00370 Hom.: 1

Bravo AF: 0.00614

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.0
Dann	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs141152269; hg19: chr9-137710829;