rs1799798

Positions:

• chr16-13920421-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+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,488,370 control chromosomes in the GnomAD database, including 8,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (726 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8050 hom.)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.831

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]

ERCC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-13920421-G-A is Benign according to our data. Variant chr16-13920421-G-A is described in ClinVar as [Benign]. Clinvar id is 1177770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.207+49G>A		intron_variant		ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.207+49G>A		intron_variant			XP_011520726.1
LOC105371093	XR_007064999.1	n.82+6104C>T		intron_variant
LOC105371093	XR_007065000.1	n.82+6104C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.207+49G>A		intron_variant		1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12248 AN: 152184 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.125 AC: 17108 AN: 137318 Hom.: 1441 AF XY: 0.127 AC XY: 9450 AN XY: 74686

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.0290

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0902

Gnomad OTH exome AF: 0.0966

GnomAD4 exome AF: 0.100 AC: 133610 AN: 1336068 Hom.: 8050 Cov.: 23 AF XY: 0.103 AC XY: 68455 AN XY: 662346

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.0295

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0919

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.0804 AC: 12248 AN: 152302 Hom.: 726 Cov.: 32 AF XY: 0.0858 AC XY: 6390 AN XY: 74476

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0796 Hom.: 148

Bravo AF: 0.0755

Asia WGS AF: 0.178 AC: 615 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.5
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799798; hg19: chr16-14014278;