rs762521

chr16-13920383-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005236.3(ERCC4):c.207+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,554,340 control chromosomes in the GnomAD database, including 55,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4387 hom., cov: 33)
  • Exomes 𝑓: 0.27 (51362 hom.)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.67

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

LOC105371093 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-13920383-G-A is Benign according to our data. Variant chr16-13920383-G-A is described in ClinVar as [Benign]. Clinvar id is 259683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.207+11G>A		intron_variant		ENST00000311895.8
LOC105371093	XR_007065000.1	n.82+6142C>T		intron_variant, non_coding_transcript_variant
ERCC4	XM_011522424.4	c.207+11G>A		intron_variant
LOC105371093	XR_007064999.1	n.82+6142C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.207+11G>A		intron_variant		1	NM_005236.3	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35270 AN: 152074 Hom.: 4383 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.250 AC: 40797 AN: 162972 Hom.: 5338 AF XY: 0.257 AC XY: 22955 AN XY: 89406

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.296

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.268 AC: 375739 AN: 1402148 Hom.: 51362 Cov.: 34 AF XY: 0.269 AC XY: 186949 AN XY: 694438

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.232 AC: 35291 AN: 152192 Hom.: 4387 Cov.: 33 AF XY: 0.229 AC XY: 17063 AN XY: 74402

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.263

Alfa AF: 0.266 Hom.: 985

Bravo AF: 0.226

Asia WGS AF: 0.278 AC: 967 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Xeroderma pigmentosum, group F Benign:3

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cockayne syndrome;C0268140:Xeroderma pigmentosum, group F;C3808988:Fanconi anemia complementation group Q Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

XFE progeroid syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Fanconi anemia complementation group Q Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	12
Dann	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs762521; hg19: chr16-14014240; COSMIC: COSV61311241; COSMIC: COSV61311241;