9-134842386-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.*83C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 1,532,632 control chromosomes in the GnomAD database, including 417,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44058 hom., cov: 32)
  • Exomes 𝑓: 0.73 (373297 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0550

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=-0.88).
• BP6: Variant 9-134842386-C-T is Benign according to our data. Variant chr9-134842386-C-T is described in ClinVar as [Benign]. Clinvar id is 365741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.*83C>T		3_prime_UTR_variant	66/66	ENST00000371817.8
LOC101448202	NR_103451.2	n.71-22177G>A		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.*83C>T		3_prime_UTR_variant	66/66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.*83C>T		3_prime_UTR_variant	66/66	1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.*83C>T		3_prime_UTR_variant	66/66	2		A2

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115116 AN: 152020 Hom.: 44011 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.734 AC: 1013449 AN: 1380494 Hom.: 373297 Cov.: 21 AF XY: 0.735 AC XY: 505199 AN XY: 687364

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.766

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.754

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.743

GnomAD4 genome AF: 0.757 AC: 115215 AN: 152138 Hom.: 44058 Cov.: 32 AF XY: 0.754 AC XY: 56079 AN XY: 74350

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.751

Alfa AF: 0.742 Hom.: 40403

Bravo AF: 0.746

Asia WGS AF: 0.709 AC: 2468 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Ehlers-Danlos syndrome type 7A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.1
Dann	Benign	0.86

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: rs13946; hg19: chr9-137734232; COSMIC: COSV65676260;