Variant rs3196378 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.686

Variant links:

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]

COL5A1 links:

LOC101448202 (HGNC:):

LOC101448202 links:

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ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE
COL5A1	NM_000093.5 linkuse as main transcript	c.*733C>A	3_prime_UTR_variant	66/66	ENST00000371817.8
LOC101448202	NR_103451.2 linkuse as main transcript	n.71-22827G>T	intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1 linkuse as main transcript	c.*733C>A	3_prime_UTR_variant	66/66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8 linkuse as main transcript	c.*733C>A		3_prime_UTR_variant	66/66	1	NM_000093.5	P4	P20908-1
COL5A1	ENST00000371820.4 linkuse as main transcript	c.*733C>A		3_prime_UTR_variant	66/66	2		A2	P20908-2

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

63800

AN:

151230

Hom.:

15982

Cov.:

show subpopulations

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.:

AF XY:

0.679

AC XY:

182

AN XY:

268

show subpopulations

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.:

AF XY:

0.421

AC XY:

31135

AN XY:

73876

show subpopulations

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fibromuscular dysplasia, multifocal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

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 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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over