chr9-134690878-C-T

Position:

• chr9-134690878-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371817.8(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 ENST00000371817.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.110-34C>T		intron_variant		ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.110-34C>T		intron_variant			NP_001265003.1
COL5A1	XM_017014266.3	c.110-34C>T		intron_variant			XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.110-34C>T		intron_variant		1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.110-34C>T		intron_variant		2		ENSP00000360885	A2
COL5A1	ENST00000464187.1	n.296-34C>T		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0615 AC: 15168 AN: 246662 Hom.: 542 AF XY: 0.0617 AC XY: 8269 AN XY: 134038

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 SAS exome AF: 0.0351

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

Gnomad4 AFR exome AF: 0.0670

Gnomad4 AMR exome AF: 0.0439

Gnomad4 ASJ exome AF: 0.0690

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0367

Gnomad4 FIN exome AF: 0.0841

Gnomad4 NFE exome AF: 0.0783

Gnomad4 OTH exome AF: 0.0697

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

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0861

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0741 Hom.: 130

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fibromuscular dysplasia, multifocal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

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	-0.85
CADD	Benign	0.0090
DANN	Benign	0.72

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: rs72772548; hg19: chr9-137582724;