rs873601

Variant names:

• chr13-102875987-G-A
• rs873601
• NM_000123.4:c.*84G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-102875987-G-A
• chr13-102875987-G-C

Variant summary

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

The NM_000123.4(ERCC5):​c.*84G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 1,513,566 control chromosomes in the GnomAD database, including 371,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29263 hom., cov: 33)
  • Exomes 𝑓: 0.70 (342074 hom.)
• Consequence: ERCC5 NM_000123.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0380
• Publications: 83 publications found

Genes affected

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-102875987-G-A is Benign according to our data. Variant chr13-102875987-G-A is described in ClinVar as Benign. ClinVar VariationId is 310945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000123.4. 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
	ERCC5	NM_000123.4	MANE Select	c.*84G>A		3_prime_UTR	Exon 15 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.*84G>A		3_prime_UTR	Exon 23 of 23	NP_001191354.2	R4GMW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	ENST00000652225.2	MANE Select	c.*84G>A		3_prime_UTR	Exon 15 of 15	ENSP00000498881.2	P28715-1
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.*84G>A		3_prime_UTR	Exon 25 of 25	ENSP00000491742.1	R4GMW8
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.*84G>A		3_prime_UTR	Exon 24 of 24	ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90802 AN: 152046 Hom.: 29260 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.704 AC: 958649 AN: 1361402 Hom.: 342074 Cov.: 21 AF XY: 0.707 AC XY: 479955 AN XY: 678612

African (AFR) AF: 0.332 AC: 10156 AN: 30612

American (AMR) AF: 0.633 AC: 26569 AN: 41966

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 17521 AN: 25372

East Asian (EAS) AF: 0.461 AC: 17012 AN: 36906

South Asian (SAS) AF: 0.740 AC: 60178 AN: 81352

European-Finnish (FIN) AF: 0.649 AC: 24258 AN: 37404

Middle Eastern (MID) AF: 0.672 AC: 3657 AN: 5446

European-Non Finnish (NFE) AF: 0.728 AC: 760521 AN: 1045104

Other (OTH) AF: 0.677 AC: 38777 AN: 57240

GnomAD4 genome AF: 0.597 AC: 90830 AN: 152164 Hom.: 29263 Cov.: 33 AF XY: 0.597 AC XY: 44427 AN XY: 74394

African (AFR) AF: 0.342 AC: 14197 AN: 41468

American (AMR) AF: 0.647 AC: 9901 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2431 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2559 AN: 5186

South Asian (SAS) AF: 0.728 AC: 3518 AN: 4830

European-Finnish (FIN) AF: 0.644 AC: 6822 AN: 10586

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49220 AN: 68006

Other (OTH) AF: 0.613 AC: 1297 AN: 2116

Alfa AF: 0.683 Hom.: 136861

Bravo AF: 0.578

Asia WGS AF: 0.570 AC: 1984 AN: 3478

ClinVar

ClinVar submissions

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	-0.82
CADD	Benign	2.1
DANN	Benign	0.93
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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: rs873601; hg19: chr13-103528337;