9-134843428-A-T

Position:

• chr9-134843428-A-T

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.*1125A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,326 control chromosomes in the GnomAD database, including 33,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33754 hom., cov: 30)
  • Exomes 𝑓: 0.76 (157 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.384

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=-0.96).
• BP6: Variant 9-134843428-A-T is Benign according to our data. Variant chr9-134843428-A-T is described in ClinVar as [Benign]. Clinvar id is 365769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.*1125A>T		3_prime_UTR_variant	66/66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.*1125A>T		3_prime_UTR_variant	66/66		NP_001265003.1
LOC101448202	NR_103451.2	n.71-23219T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.*1125A>T		3_prime_UTR_variant	66/66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.*1125A>T		3_prime_UTR_variant	66/66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100671 AN: 151664 Hom.: 33739 Cov.: 30

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.756 AC: 411 AN: 544 Hom.: 157 Cov.: 0 AF XY: 0.770 AC XY: 251 AN XY: 326

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.770

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.664 AC: 100730 AN: 151782 Hom.: 33754 Cov.: 30 AF XY: 0.661 AC XY: 48998 AN XY: 74146

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.679

Alfa AF: 0.587 Hom.: 1695

Bravo AF: 0.647

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Ehlers-Danlos syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 16, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.49

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: rs1134170; hg19: chr9-137735274; COSMIC: COSV65668680;