rs72772548

Variant names:

• chr9-134690878-C-T
• rs72772548
• NM_000093.5:c.110-34C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.110-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,612,728 control chromosomes in the GnomAD database, including 4,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (426 hom., cov: 33)
  • Exomes 𝑓: 0.072 (4051 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.28
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-134690878-C-T is Benign according to our data. Variant chr9-134690878-C-T is described in ClinVar as [Benign]. Clinvar id is 255047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.110-34C>T		intron_variant	Intron 1 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.110-34C>T		intron_variant	Intron 1 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.110-34C>T		intron_variant	Intron 1 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.110-34C>T		intron_variant	Intron 1 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.110-34C>T		intron_variant	Intron 1 of 65	2		ENSP00000360885.4
COL5A1	ENST00000464187.1	n.296-34C>T		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10384 AN: 152154 Hom.: 423 Cov.: 33

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0745

GnomAD2 exomes AF: 0.0615 AC: 15168 AN: 246662 AF XY: 0.0617

Gnomad AFR exome AF: 0.0673

Gnomad AMR exome AF: 0.0433

Gnomad ASJ exome AF: 0.0709

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0835

Gnomad NFE exome AF: 0.0782

Gnomad OTH exome AF: 0.0715

GnomAD4 exome AF: 0.0721 AC: 105243 AN: 1460456 Hom.: 4051 Cov.: 32 AF XY: 0.0712 AC XY: 51711 AN XY: 726504

African (AFR) AF: 0.0670 AC: 2243 AN: 33466

American (AMR) AF: 0.0439 AC: 1961 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 1803 AN: 26130

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0367 AC: 3163 AN: 86224

European-Finnish (FIN) AF: 0.0841 AC: 4400 AN: 52320

Middle Eastern (MID) AF: 0.0686 AC: 395 AN: 5754

European-Non Finnish (NFE) AF: 0.0783 AC: 87065 AN: 1111788

Other (OTH) AF: 0.0697 AC: 4208 AN: 60368

GnomAD4 genome AF: 0.0683 AC: 10397 AN: 152272 Hom.: 426 Cov.: 33 AF XY: 0.0674 AC XY: 5021 AN XY: 74462

African (AFR) AF: 0.0645 AC: 2679 AN: 41566

American (AMR) AF: 0.0601 AC: 919 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5172

South Asian (SAS) AF: 0.0335 AC: 162 AN: 4830

European-Finnish (FIN) AF: 0.0861 AC: 913 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0777 AC: 5283 AN: 68006

Other (OTH) AF: 0.0737 AC: 156 AN: 2116

Alfa AF: 0.0738 Hom.: 132

Bravo AF: 0.0666

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0090
DANN	Benign	0.72
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72772548; hg19: chr9-137582724;