rs2296147

Variant names:

• chr13-102846025-T-A
• rs2296147
• ENST00000639435.1:c.1451-6093T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-102846025-T-A
• chr13-102846025-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000639435.1(BIVM-ERCC5):​c.1451-6093T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 409,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: BIVM-ERCC5 ENST00000639435.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 0 publications found

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]

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

ENSG00000305730 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM-ERCC5	NM_001204425.2	c.1451-6093T>A		intron_variant	Intron 9 of 22		NP_001191354.2
ERCC5	NM_000123.4	c.-242T>A		upstream_gene_variant		ENST00000652225.2	NP_000114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIVM-ERCC5	ENST00000639435.1	c.1451-6093T>A		intron_variant	Intron 11 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.764-6093T>A		intron_variant	Intron 10 of 23	5		ENSP00000492684.1
ERCC5	ENST00000652225.2	c.-242T>A		upstream_gene_variant			NM_000123.4	ENSP00000498881.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000244 AC: 10 AN: 409146 Hom.: 0 Cov.: 2 AF XY: 0.0000373 AC XY: 8 AN XY: 214426

African (AFR) AF: 0.00 AC: 0 AN: 11684

American (AMR) AF: 0.00 AC: 0 AN: 16280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12814

East Asian (EAS) AF: 0.00 AC: 0 AN: 29704

South Asian (SAS) AF: 0.000232 AC: 9 AN: 38780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1844

European-Non Finnish (NFE) AF: 0.00000406 AC: 1 AN: 246442

Other (OTH) AF: 0.00 AC: 0 AN: 24094

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		-0.26
PromoterAI		0.032	Neutral

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: rs2296147; hg19: chr13-103498375;