rs55748801

Positions:

• chr9-134842493-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.*190G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00898 in 684,656 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (61 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02

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=-0.7).
• BP6: Variant 9-134842493-G-A is Benign according to our data. Variant chr9-134842493-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 365744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00575 (875/152268) while in subpopulation SAS AF= 0.027 (130/4818). AF 95% confidence interval is 0.0232. There are 9 homozygotes in gnomad4. There are 429 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 875 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.*190G>A		3_prime_UTR_variant	66/66	ENST00000371817.8	NP_000084.3
LOC101448202	NR_103451.2	n.71-22284C>T		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.*190G>A		3_prime_UTR_variant	66/66		NP_001265003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.*190G>A		3_prime_UTR_variant	66/66	1	NM_000093.5	ENSP00000360882	P4
COL5A1	ENST00000371820.4	c.*190G>A		3_prime_UTR_variant	66/66	2		ENSP00000360885	A2

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 869 AN: 152150 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00657

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.00991 AC: 5274 AN: 532388 Hom.: 61 Cov.: 6 AF XY: 0.0113 AC XY: 3157 AN XY: 279638

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.00547

Gnomad4 NFE exome AF: 0.00863

Gnomad4 OTH exome AF: 0.00779

GnomAD4 genome AF: 0.00575 AC: 875 AN: 152268 Hom.: 9 Cov.: 32 AF XY: 0.00576 AC XY: 429 AN XY: 74444

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00640

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00832

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00847 Hom.: 3

Bravo AF: 0.00471

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ehlers-Danlos syndrome type 7A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely 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	-0.70
CADD	Benign	12
DANN	Benign	0.90

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: rs55748801; hg19: chr9-137734339;