9-134812759-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000093.5(COL5A1):​c.3852+47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000778 in 969,632 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0000082 ( 0 hom., cov: 28)
Exomes 𝑓: 0.00089 ( 1 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.91
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 9-134812759-A-T is Benign according to our data. Variant chr9-134812759-A-T is described in ClinVar as [Benign]. Clinvar id is 255083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 753 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL5A1NM_000093.5 linkuse as main transcriptc.3852+47A>T intron_variant ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkuse as main transcriptc.3852+47A>T intron_variant NP_001265003.1 B2ZZ86Q59EE7
COL5A1XM_017014266.3 linkuse as main transcriptc.3852+47A>T intron_variant XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkuse as main transcriptc.3852+47A>T intron_variant 1 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkuse as main transcriptc.3852+47A>T intron_variant 2 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
AF:
0.00000817
AC:
1
AN:
122374
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000173
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000889
AC:
753
AN:
847258
Hom.:
1
Cov.:
12
AF XY:
0.000804
AC XY:
347
AN XY:
431812
show subpopulations
Gnomad4 AFR exome
AF:
0.00118
Gnomad4 AMR exome
AF:
0.0000309
Gnomad4 ASJ exome
AF:
0.000211
Gnomad4 EAS exome
AF:
0.0000644
Gnomad4 SAS exome
AF:
0.000231
Gnomad4 FIN exome
AF:
0.0000504
Gnomad4 NFE exome
AF:
0.00111
Gnomad4 OTH exome
AF:
0.000866
GnomAD4 genome
AF:
0.00000817
AC:
1
AN:
122374
Hom.:
0
Cov.:
28
AF XY:
0.0000167
AC XY:
1
AN XY:
59798
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000173
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0149
Hom.:
1

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.095
DANN
Benign
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111564392; hg19: chr9-137704605; API