chr9-134825744-G-A

Position:

• chr9-134825744-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000093.5(COL5A1):​c.4955-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,260,514 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (7 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.46

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=-0.78).
• BP6: Variant 9-134825744-G-A is Benign according to our data. Variant chr9-134825744-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00434 (661/152340) while in subpopulation AFR AF= 0.0148 (616/41586). AF 95% confidence interval is 0.0138. There are 4 homozygotes in gnomad4. There are 307 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 661 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.4955-48G>A		intron_variant		ENST00000371817.8
LOC101448202	NR_103451.2	n.71-5535C>T		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.4955-48G>A		intron_variant
COL5A1	XM_017014266.3	c.4955-48G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.4955-48G>A		intron_variant		1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.4955-48G>A		intron_variant		2		A2
COL5A1	ENST00000460264.5	n.423-48G>A		intron_variant, non_coding_transcript_variant		3
COL5A1	ENST00000465877.1	n.135-48G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 657 AN: 152222 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00130 AC: 316 AN: 243214 Hom.: 3 AF XY: 0.000988 AC XY: 130 AN XY: 131594

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.000707

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000336

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.000841

GnomAD4 exome AF: 0.000608 AC: 674 AN: 1108174 Hom.: 7 Cov.: 14 AF XY: 0.000501 AC XY: 284 AN XY: 567102

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.00115

Gnomad4 ASJ exome AF: 0.000975

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000384

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000895

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00434 AC: 661 AN: 152340 Hom.: 4 Cov.: 33 AF XY: 0.00412 AC XY: 307 AN XY: 74500

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00421 Hom.: 0

Bravo AF: 0.00493

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

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	-0.78
CADD	Benign	0.70
DANN	Benign	0.87

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: rs60879388; hg19: chr9-137717590;