9-134844698-G-T

Position:

• chr9-134844698-G-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.*2395G>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 0.766 in 152,208 control chromosomes in the GnomAD database, including 45,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45071 hom., cov: 34)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100

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=-0.9).
• BP6: Variant 9-134844698-G-T is Benign according to our data. Variant chr9-134844698-G-T is described in ClinVar as [Benign]. Clinvar id is 365791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.*2395G>T		3_prime_UTR_variant	66/66	ENST00000371817.8
LOC101448202	NR_103451.2	n.71-24489C>A		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.*2395G>T		3_prime_UTR_variant	66/66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.*2395G>T		3_prime_UTR_variant	66/66	1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.*2395G>T		3_prime_UTR_variant	66/66	2		A2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116465 AN: 152084 Hom.: 45020 Cov.: 34

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.766 AC: 116572 AN: 152202 Hom.: 45071 Cov.: 34 AF XY: 0.762 AC XY: 56720 AN XY: 74402

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.763

Alfa AF: 0.747 Hom.: 49395

Bravo AF: 0.757

Asia WGS AF: 0.720 AC: 2506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.58

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: rs4504708; hg19: chr9-137736544;