rs17655

Variant names:

• chr13-102875652-G-C
• rs17655
• NM_000123.4:c.3310G>C

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.4672G>C​(p.Asp1558His) variant causes a missense change. The variant allele was found at a frequency of 0.243 in 1,613,874 control chromosomes in the GnomAD database, including 52,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7842 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44770 hom.)
• Consequence: BIVM-ERCC5 NM_001204425.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10 O:1
• Conservation: PhyloP100: 5.18
• Publications: 328 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 (MetaRNN=2.9867887E-4).
• BP6: Variant 13-102875652-G-C is Benign according to our data. Variant chr13-102875652-G-C is described in ClinVar as Benign. ClinVar VariationId is 129011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	NM_000123.4	MANE Select	c.3310G>C	p.Asp1104His	missense	Exon 15 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.4672G>C	p.Asp1558His	missense	Exon 23 of 23	NP_001191354.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	ENST00000652225.2	MANE Select	c.3310G>C	p.Asp1104His	missense	Exon 15 of 15	ENSP00000498881.2
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.4672G>C	p.Asp1558His	missense	Exon 25 of 25	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.3985G>C	p.Asp1329His	missense	Exon 24 of 24	ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45995 AN: 151936 Hom.: 7831 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.278 AC: 69697 AN: 251078 AF XY: 0.267

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.494

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.237 AC: 346299 AN: 1461818 Hom.: 44770 Cov.: 43 AF XY: 0.235 AC XY: 171187 AN XY: 727190

African (AFR) AF: 0.464 AC: 15528 AN: 33478

American (AMR) AF: 0.325 AC: 14538 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7368 AN: 26136

East Asian (EAS) AF: 0.529 AC: 21013 AN: 39698

South Asian (SAS) AF: 0.228 AC: 19687 AN: 86246

European-Finnish (FIN) AF: 0.243 AC: 12970 AN: 53420

Middle Eastern (MID) AF: 0.298 AC: 1719 AN: 5768

European-Non Finnish (NFE) AF: 0.214 AC: 237727 AN: 1111972

Other (OTH) AF: 0.261 AC: 15749 AN: 60384

GnomAD4 genome AF: 0.303 AC: 46051 AN: 152056 Hom.: 7842 Cov.: 32 AF XY: 0.303 AC XY: 22496 AN XY: 74338

African (AFR) AF: 0.453 AC: 18764 AN: 41460

American (AMR) AF: 0.292 AC: 4458 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 949 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2547 AN: 5176

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4818

European-Finnish (FIN) AF: 0.240 AC: 2533 AN: 10562

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14725 AN: 67972

Other (OTH) AF: 0.305 AC: 645 AN: 2114

Alfa AF: 0.244 Hom.: 3790

Bravo AF: 0.320

TwinsUK AF: 0.207 AC: 766

ALSPAC AF: 0.210 AC: 809

ESP6500AA AF: 0.456 AC: 2009

ESP6500EA AF: 0.229 AC: 1968

ExAC AF: 0.277 AC: 33673

Asia WGS AF: 0.388 AC: 1348 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.230

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Xeroderma pigmentosum, group G (4)
-	-	3	not provided (3)
-	-	2	not specified (3)
-	-	1	Cerebrooculofacioskeletal syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.026
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.00030	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.2
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.037	D
Polyphen		0.99	D
Vest4		0.29
MPC		0.52
ClinPred		0.017	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.26
Mutation Taster		=85/15	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: rs17655; hg19: chr13-103528002; COSMIC: COSV63243750; COSMIC: COSV63243750;