rs4150386

Variant names:

• chr13-102875178-A-C
• rs4150386
• NM_000123.4:c.2965-129A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-102875178-A-C
• chr13-102875178-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000123.4(ERCC5):​c.2965-129A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,077,046 control chromosomes in the GnomAD database, including 6,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (628 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6307 hom.)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180
• Publications: 13 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-102875178-A-C is Benign according to our data. Variant chr13-102875178-A-C is described in ClinVar as Benign. ClinVar VariationId is 1268900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-129A>C		intron_variant	Intron 14 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-129A>C		intron_variant	Intron 22 of 22		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.2965-129A>C		intron_variant	Intron 14 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4327-129A>C		intron_variant	Intron 24 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3640-129A>C		intron_variant	Intron 23 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12448 AN: 152182 Hom.: 628 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0864

GnomAD4 exome AF: 0.110 AC: 101661 AN: 924746 Hom.: 6307 AF XY: 0.109 AC XY: 51238 AN XY: 468542

African (AFR) AF: 0.0173 AC: 367 AN: 21190

American (AMR) AF: 0.0672 AC: 1653 AN: 24614

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2281 AN: 18424

East Asian (EAS) AF: 0.00846 AC: 281 AN: 33230

South Asian (SAS) AF: 0.0747 AC: 4359 AN: 58336

European-Finnish (FIN) AF: 0.0893 AC: 3512 AN: 39336

Middle Eastern (MID) AF: 0.0844 AC: 251 AN: 2974

European-Non Finnish (NFE) AF: 0.124 AC: 84839 AN: 685130

Other (OTH) AF: 0.0992 AC: 4118 AN: 41512

GnomAD4 genome AF: 0.0817 AC: 12447 AN: 152300 Hom.: 628 Cov.: 33 AF XY: 0.0802 AC XY: 5972 AN XY: 74466

African (AFR) AF: 0.0204 AC: 848 AN: 41574

American (AMR) AF: 0.0806 AC: 1234 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.00810 AC: 42 AN: 5186

South Asian (SAS) AF: 0.0729 AC: 352 AN: 4828

European-Finnish (FIN) AF: 0.0930 AC: 987 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8197 AN: 68008

Other (OTH) AF: 0.0860 AC: 182 AN: 2116

Alfa AF: 0.0968 Hom.: 208

Bravo AF: 0.0781

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.78
PhyloP100		0.18
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: rs4150386; hg19: chr13-103527528;