rs112712705

chr9-134825776-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):c.4955-16C>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 0.00323 in 1,567,832 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (58 hom., cov: 34)
  • Exomes 𝑓: 0.0019 (63 hom.)
• Consequence: COL5A1 NM_000093.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.456

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]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-134825776-C-T is Benign according to our data. Variant chr9-134825776-C-T is described in ClinVar as [Benign]. Clinvar id is 136905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-134825776-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.4955-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371817.8
LOC101448202	NR_103451.2	n.71-5567G>A		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.4955-16C>T		splice_polypyrimidine_tract_variant, intron_variant
COL5A1	XM_017014266.3	c.4955-16C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.4955-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.4955-16C>T		splice_polypyrimidine_tract_variant, intron_variant		2		A2
COL5A1	ENST00000460264.5	n.423-16C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3
COL5A1	ENST00000465877.1	n.135-16C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2412 AN: 152216 Hom.: 57 Cov.: 34

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00454 AC: 1138 AN: 250890 Hom.: 19 AF XY: 0.00324 AC XY: 440 AN XY: 135658

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000441

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00187 AC: 2649 AN: 1415498 Hom.: 63 Cov.: 23 AF XY: 0.00161 AC XY: 1137 AN XY: 706808

Gnomad4 AFR exome AF: 0.0542

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000259

Gnomad4 FIN exome AF: 0.000208

Gnomad4 NFE exome AF: 0.000322

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.0159 AC: 2420 AN: 152334 Hom.: 58 Cov.: 34 AF XY: 0.0148 AC XY: 1106 AN XY: 74488

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00912 Hom.: 10

Bravo AF: 0.0176

Asia WGS AF: 0.00462 AC: 16 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	PreventionGenetics, part of Exact Sciences	-	- -
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	GeneDx	Apr 15, 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	Jan 31, 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

Aug 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	2.3
Dann	Benign	0.89

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: rs112712705; hg19: chr9-137717622;