rs3196378

chr9-134843036-C-Achr9-134843036-C-Gchr9-134843036-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.*733C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,780 control chromosomes in the GnomAD database, including 16,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15979 hom., cov: 28)
  • Exomes 𝑓: 0.69 (105 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.686

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=-0.83).
• BP6: Variant 9-134843036-C-A is Benign according to our data. Variant chr9-134843036-C-A is described in ClinVar as [Benign]. Clinvar id is 365760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.*733C>A		3_prime_UTR_variant	66/66	ENST00000371817.8
LOC101448202	NR_103451.2	n.71-22827G>T		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.*733C>A		3_prime_UTR_variant	66/66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.*733C>A		3_prime_UTR_variant	66/66	1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.*733C>A		3_prime_UTR_variant	66/66	2		A2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63800 AN: 151230 Hom.: 15982 Cov.: 28

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.687 AC: 298 AN: 434 Hom.: 105 Cov.: 0 AF XY: 0.679 AC XY: 182 AN XY: 268

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.697

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.421 AC: 63790 AN: 151346 Hom.: 15979 Cov.: 28 AF XY: 0.421 AC XY: 31135 AN XY: 73876

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.472

Alfa AF: 0.454 Hom.: 6388

Bravo AF: 0.395

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Ehlers-Danlos syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 16, 2022

- -

Ehlers-Danlos syndrome, classic type Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 03, 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	-0.83
Cadd	Benign	0.83
Dann	Benign	0.77

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: rs3196378; hg19: chr9-137734882; COSMIC: COSV65667236;