13-102845830-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000639435.1(BIVM-ERCC5):c.1450+6027C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 253,814 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 257 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 48 hom. )

Consequence

BIVM-ERCC5
ENST00000639435.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66

Publications

1 publications found

Variant links:

Genes affected

BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 links:

ENSG00000305730 (HGNC:):

ENSG00000305730 links:

ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

ERCC5 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group G
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
cerebrooculofacioskeletal syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
COFS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum-Cockayne syndrome complex
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERCC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 13-102845830-C-A is Benign according to our data. Variant chr13-102845830-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 369032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM-ERCC5	NM_001204425.2 link	c.1450+6027C>A		intron_variant	Intron 9 of 22		NP_001191354.2	R4GMW8Q59FZ7
ERCC5	NM_000123.4 link	c.-437C>A		upstream_gene_variant		ENST00000652225.2	NP_000114.3	P28715-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BIVM-ERCC5	ENST00000639435.1 link	c.1450+6027C>A	intron_variant	Intron 11 of 24	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 link	c.763+6027C>A	intron_variant	Intron 10 of 23	5		ENSP00000492684.1	A0A1W2PS85
ERCC5	ENST00000652225.2 link	c.-437C>A	upstream_gene_variant			NM_000123.4	ENSP00000498881.2	P28715-1

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4906

AN:

152228

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0164

Gnomad SAS

AF:

0.00911

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.00863

AC:

876

AN:

101468

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

404

AN XY:

48966

show subpopulations

African (AFR)

AF:

0.117

AC:

489

AN:

4194

American (AMR)

AF:

0.00820

AC:

AN:

4266

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

5240

East Asian (EAS)

AF:

0.00668

AC:

AN:

11684

South Asian (SAS)

AF:

0.00715

AC:

AN:

4334

European-Finnish (FIN)

AF:

0.00213

AC:

AN:

1880

Middle Eastern (MID)

AF:

0.00521

AC:

AN:

576

European-Non Finnish (NFE)

AF:

0.000746

AC:

AN:

61624

Other (OTH)

AF:

0.0155

AC:

119

AN:

7670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0323

AC:

4916

AN:

152346

Hom.:

257

Cov.:

AF XY:

0.0312

AC XY:

2326

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.107

AC:

4446

AN:

41570

American (AMR)

AF:

0.0112

AC:

172

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3472

East Asian (EAS)

AF:

0.0164

AC:

AN:

5186

South Asian (SAS)

AF:

0.00911

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68032

Other (OTH)

AF:

0.0241

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

229

459

688

918

1147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 28, 2019

GeneDx

Significance: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

-0.68

CADD

Benign

1.7

(source)

DANN

Benign

0.78

PhyloP100

-1.7

PromoterAI

-0.0031

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

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13-102845830-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over