rs4150375

Variant names:

• chr13-102874767-A-G
• rs4150375
• NM_000123.4:c.2965-540A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-102874767-A-G
• chr13-102874767-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000123.4(ERCC5):​c.2965-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,184 control chromosomes in the GnomAD database, including 1,536 homozygotes. 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: 𝑓 0.12 (1536 hom., cov: 33)
  • Exomes 𝑓: 0.11 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.2965-540A>G		intron_variant	Intron 14 of 14	ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.4327-540A>G		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.2965-540A>G		intron_variant	Intron 14 of 14		NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.4327-540A>G		intron_variant	Intron 24 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.3640-540A>G		intron_variant	Intron 23 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18599 AN: 152066 Hom.: 1537 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.109 AC: 225 AN: 2064 Hom.: 18 Cov.: 0 AF XY: 0.0942 AC XY: 116 AN XY: 1232

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AF: 0.204 AC: 57 AN: 280

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1 AN: 14

East Asian (EAS) AF: 0.474 AC: 18 AN: 38

South Asian (SAS) AF: 0.131 AC: 21 AN: 160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0837 AC: 124 AN: 1482

Other (OTH) AF: 0.0588 AC: 4 AN: 68

GnomAD4 genome AF: 0.122 AC: 18611 AN: 152184 Hom.: 1536 Cov.: 33 AF XY: 0.126 AC XY: 9390 AN XY: 74390

African (AFR) AF: 0.125 AC: 5208 AN: 41530

American (AMR) AF: 0.144 AC: 2198 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2468 AN: 5160

South Asian (SAS) AF: 0.140 AC: 676 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1446 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5939 AN: 67988

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0370 Hom.: 23

Bravo AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.31
PhyloP100		-0.048
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: rs4150375; hg19: chr13-103527117;