NM_000093.5:c.4608+31T>C

Variant names:

• chr9-134822181-T-C
• rs9697186
• NM_000093.5:c.4608+31T>C

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.4608+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,301,564 control chromosomes in the GnomAD database, including 253,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (31951 hom., cov: 31)
  • Exomes 𝑓: 0.65 (221440 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.47

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=-0.89).
• BP6: Variant 9-134822181-T-C is Benign according to our data. Variant chr9-134822181-T-C is described in ClinVar as [Benign]. Clinvar id is 255089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.4608+31T>C		intron_variant	Intron 59 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.4608+31T>C		intron_variant	Intron 59 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.4608+31T>C		intron_variant	Intron 59 of 64		XP_016869755.1
LOC101448202	NR_103451.2	n.71-1972A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.4608+31T>C		intron_variant	Intron 59 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.4608+31T>C		intron_variant	Intron 59 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.645 AC: 96055 AN: 148896 Hom.: 31901 Cov.: 31

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.629

GnomAD3 exomes AF: 0.557 AC: 138253 AN: 248360 Hom.: 39675 AF XY: 0.552 AC XY: 74145 AN XY: 134434

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.524

Gnomad SAS exome AF: 0.482

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.652 AC: 751997 AN: 1152542 Hom.: 221440 Cov.: 19 AF XY: 0.645 AC XY: 376583 AN XY: 584074

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.645 AC: 96160 AN: 149022 Hom.: 31951 Cov.: 31 AF XY: 0.635 AC XY: 46103 AN XY: 72600

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.630

Alfa AF: 0.600 Hom.: 5063

Bravo AF: 0.642

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.89
CADD	Benign	0.037
DANN	Benign	0.37

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: rs9697186; hg19: chr9-137714027; COSMIC: COSV65666845; COSMIC: COSV65666845;