chr9-134844804-T-C

Variant names:

• chr9-134844804-T-C
• rs3128575
• NM_000093.5:c.*2501T>C

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.*2501T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,154 control chromosomes in the GnomAD database, including 31,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31371 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: COL5A1 NM_000093.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0360
• Publications: 13 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=-0.63).
• BP6: Variant 9-134844804-T-C is Benign according to our data. Variant chr9-134844804-T-C is described in ClinVar as Benign. ClinVar VariationId is 365795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 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.*2501T>C		3_prime_UTR	Exon 66 of 66	NP_000084.3
	COL5A1	NM_001278074.1		c.*2501T>C		3_prime_UTR	Exon 66 of 66	NP_001265003.1	P20908-2
	LOC101448202	NR_103451.2		n.71-24595A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.*2501T>C		3_prime_UTR	Exon 66 of 66	ENSP00000360882.3	P20908-1
	COL5A1	ENST00000371820.4	TSL:2	c.*2501T>C		3_prime_UTR	Exon 66 of 66	ENSP00000360885.4	P20908-2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96414 AN: 152036 Hom.: 31362 Cov.: 34

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.661

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.634 AC: 96459 AN: 152154 Hom.: 31371 Cov.: 34 AF XY: 0.632 AC XY: 46969 AN XY: 74372

African (AFR) AF: 0.508 AC: 21078 AN: 41490

American (AMR) AF: 0.591 AC: 9046 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2581 AN: 3466

East Asian (EAS) AF: 0.454 AC: 2344 AN: 5164

South Asian (SAS) AF: 0.638 AC: 3079 AN: 4826

European-Finnish (FIN) AF: 0.742 AC: 7863 AN: 10598

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48400 AN: 67998

Other (OTH) AF: 0.664 AC: 1399 AN: 2108

Alfa AF: 0.686 Hom.: 60537

Bravo AF: 0.613

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome type 7A (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		-0.036
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: rs3128575; hg19: chr9-137736650;