13-102845848-A-G

Variant names:

• chr13-102845848-A-G
• rs751402
• ENST00000639435.1:c.1450+6045A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204425.2(BIVM-ERCC5):​c.1450+6045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 258,432 control chromosomes in the GnomAD database, including 76,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43735 hom., cov: 34)
  • Exomes 𝑓: 0.78 (32549 hom.)
• Consequence: BIVM-ERCC5 NM_001204425.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.57
• Publications: 102 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-102845848-A-G is Benign according to our data. Variant chr13-102845848-A-G is described in ClinVar as Benign. ClinVar VariationId is 310903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204425.2. 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
	BIVM-ERCC5	NM_001204425.2		c.1450+6045A>G		intron	N/A	NP_001191354.2
	ERCC5	NM_000123.4	MANE Select	c.-419A>G		upstream_gene	N/A	NP_000114.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.1450+6045A>G		intron	N/A	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.763+6045A>G		intron	N/A	ENSP00000492684.1
	ERCC5	ENST00000535557.5	TSL:5	n.8A>G		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114866 AN: 152044 Hom.: 43702 Cov.: 34

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.777 AC: 82596 AN: 106270 Hom.: 32549 Cov.: 0 AF XY: 0.779 AC XY: 40153 AN XY: 51518

African (AFR) AF: 0.681 AC: 3024 AN: 4440

American (AMR) AF: 0.650 AC: 2768 AN: 4260

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 4594 AN: 5488

East Asian (EAS) AF: 0.644 AC: 7854 AN: 12202

South Asian (SAS) AF: 0.716 AC: 2978 AN: 4160

European-Finnish (FIN) AF: 0.785 AC: 1832 AN: 2334

Middle Eastern (MID) AF: 0.807 AC: 502 AN: 622

European-Non Finnish (NFE) AF: 0.814 AC: 52773 AN: 64806

Other (OTH) AF: 0.788 AC: 6271 AN: 7958

GnomAD4 genome AF: 0.755 AC: 114950 AN: 152162 Hom.: 43735 Cov.: 34 AF XY: 0.753 AC XY: 56042 AN XY: 74400

African (AFR) AF: 0.687 AC: 28519 AN: 41516

American (AMR) AF: 0.681 AC: 10414 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2984 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3230 AN: 5148

South Asian (SAS) AF: 0.715 AC: 3450 AN: 4828

European-Finnish (FIN) AF: 0.797 AC: 8430 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55338 AN: 68010

Other (OTH) AF: 0.764 AC: 1617 AN: 2116

Alfa AF: 0.791 Hom.: 127559

Bravo AF: 0.745

Asia WGS AF: 0.700 AC: 2436 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Xeroderma pigmentosum, group G (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-1.6
PromoterAI		0.082	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751402; hg19: chr13-103498198;