rs3196378

Variant names:

• chr9-134843036-C-A
• rs3196378
• NM_000093.5:c.*733C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134843036-C-A
• chr9-134843036-C-G
• chr9-134843036-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000093.5(COL5A1):​c.*733C>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 0.422 in 151,780 control chromosomes in the GnomAD database, including 16,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15979 hom., cov: 28)
  • Exomes 𝑓: 0.69 (105 hom.)
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.686
• Publications: 22 publications found

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]

COL5A1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, ClinGen, Orphanet
• Ehlers-Danlos syndrome, classic type, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC101448202 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-134843036-C-A is Benign according to our data. Variant chr9-134843036-C-A is described in ClinVar as Benign. ClinVar VariationId is 365760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.*733C>A		3_prime_UTR	Exon 66 of 66	NP_000084.3
	COL5A1	NM_001278074.1		c.*733C>A		3_prime_UTR	Exon 66 of 66	NP_001265003.1	P20908-2
	LOC101448202	NR_103451.2		n.71-22827G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.*733C>A		3_prime_UTR	Exon 66 of 66	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.*733C>A		3_prime_UTR	Exon 66 of 66	ENSP00000360885.4	P20908-2
	COL5A1	ENST00000950240.1		c.*733C>A		3_prime_UTR	Exon 66 of 66	ENSP00000620299.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63800 AN: 151230 Hom.: 15982 Cov.: 28

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.687 AC: 298 AN: 434 Hom.: 105 Cov.: 0 AF XY: 0.679 AC XY: 182 AN XY: 268

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.697 AC: 290 AN: 416

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.600 AC: 6 AN: 10

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.421 AC: 63790 AN: 151346 Hom.: 15979 Cov.: 28 AF XY: 0.421 AC XY: 31135 AN XY: 73876

African (AFR) AF: 0.160 AC: 6598 AN: 41204

American (AMR) AF: 0.443 AC: 6726 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1759 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1143 AN: 5124

South Asian (SAS) AF: 0.364 AC: 1732 AN: 4752

European-Finnish (FIN) AF: 0.639 AC: 6672 AN: 10444

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37590 AN: 67870

Other (OTH) AF: 0.472 AC: 990 AN: 2098

Alfa AF: 0.456 Hom.: 10733

Bravo AF: 0.395

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome (1)
-	-	1	Ehlers-Danlos syndrome type 7A (1)
-	-	1	Ehlers-Danlos syndrome, classic type (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 1 (1)
-	-	1	Fibromuscular dysplasia, multifocal (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.83
DANN	Benign	0.77
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3196378; hg19: chr9-137734882; COSMIC: COSV65667236;