rs55748801

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000093.5(COL5A1):c.*190G>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 0.00898 in 684,656 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 61 hom. )

Consequence

COL5A1
NM_000093.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 9-134842493-G-A is Benign according to our data. Variant chr9-134842493-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 365744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00575 (875/152268) while in subpopulation SAS AF= 0.027 (130/4818). AF 95% confidence interval is 0.0232. There are 9 homozygotes in gnomad4. There are 429 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 875 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.*190G>A	3_prime_UTR_variant	Exon 66 of 66	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.*190G>A	3_prime_UTR_variant	Exon 66 of 66		NP_001265003.1	B2ZZ86Q59EE7
LOC101448202	NR_103451.2 link	n.71-22284C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.*190G>A		3_prime_UTR_variant	Exon 66 of 66	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.*190G>A		3_prime_UTR_variant	Exon 66 of 66	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

869

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00657

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00832

Gnomad OTH

AF:

0.00479

GnomAD4 exome

AF:

0.00991

AC:

5274

AN:

532388

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

3157

AN XY:

279638

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00221

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.0265

Gnomad4 FIN exome

AF:

0.00547

Gnomad4 NFE exome

AF:

0.00863

Gnomad4 OTH exome

AF:

0.00779

GnomAD4 genome

AF:

0.00575

AC:

875

AN:

152268

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00640

Gnomad4 SAS

AF:

0.0270

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00832

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00847

Hom.:

Bravo

AF:

0.00471

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.90

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