chr9-134801908-C-T

Variant names:

• chr9-134801908-C-T
• rs138964558
• NM_000093.5:c.2953-46C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000093.5(COL5A1):​c.2953-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,577,592 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (25 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (23 hom.)
• Consequence: COL5A1 NM_000093.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-134801908-C-T is Benign according to our data. Variant chr9-134801908-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1192936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00915 (1393/152250) while in subpopulation AFR AF = 0.0316 (1313/41546). AF 95% confidence interval is 0.0302. There are 25 homozygotes in GnomAd4. There are 640 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1393 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.2953-46C>T		intron_variant	Intron 37 of 65	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.2953-46C>T		intron_variant	Intron 37 of 65		NP_001265003.1
COL5A1	XM_017014266.3	c.2953-46C>T		intron_variant	Intron 37 of 64		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.2953-46C>T		intron_variant	Intron 37 of 65	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.2953-46C>T		intron_variant	Intron 37 of 65	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1392 AN: 152134 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00237 AC: 594 AN: 250118 AF XY: 0.00182

Gnomad AFR exome AF: 0.0325

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000977 AC: 1393 AN: 1425342 Hom.: 23 Cov.: 29 AF XY: 0.000855 AC XY: 608 AN XY: 711246

African (AFR) AF: 0.0353 AC: 1158 AN: 32762

American (AMR) AF: 0.00192 AC: 86 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.0000468 AC: 4 AN: 85500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52300

Middle Eastern (MID) AF: 0.000878 AC: 5 AN: 5696

European-Non Finnish (NFE) AF: 0.0000232 AC: 25 AN: 1079758

Other (OTH) AF: 0.00194 AC: 115 AN: 59218

GnomAD4 genome AF: 0.00915 AC: 1393 AN: 152250 Hom.: 25 Cov.: 32 AF XY: 0.00860 AC XY: 640 AN XY: 74448

African (AFR) AF: 0.0316 AC: 1313 AN: 41546

American (AMR) AF: 0.00431 AC: 66 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00427 Hom.: 0

Bravo AF: 0.0103

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 07, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs138964558; hg19: chr9-137693754;