rs3136146

Positions:

• chr16-13934522-G-A
• chr16-13934522-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005236.3(ERCC4):​c.1213+220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 510,630 control chromosomes in the GnomAD database, including 6,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (5054 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1923 hom.)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.193

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-13934522-G-A is Benign according to our data. Variant chr16-13934522-G-A is described in ClinVar as [Benign]. Clinvar id is 1178890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.1213+220G>A		intron_variant		ENST00000311895.8
ERCC4	XM_011522424.4	c.1351+220G>A		intron_variant
ERCC4	XM_011522427.2	c.-138+220G>A		intron_variant
ERCC4	XM_047433774.1	c.424+220G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.1213+220G>A		intron_variant		1	NM_005236.3	P1
	ENST00000570663.1	n.219+895C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27026 AN: 151964 Hom.: 5028 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0683 AC: 24505 AN: 358548 Hom.: 1923 Cov.: 0 AF XY: 0.0639 AC XY: 12217 AN XY: 191234

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.0974

Gnomad4 ASJ exome AF: 0.0954

Gnomad4 EAS exome AF: 0.000255

Gnomad4 SAS exome AF: 0.0264

Gnomad4 FIN exome AF: 0.0705

Gnomad4 NFE exome AF: 0.0590

Gnomad4 OTH exome AF: 0.0855

GnomAD4 genome AF: 0.178 AC: 27093 AN: 152082 Hom.: 5054 Cov.: 32 AF XY: 0.174 AC XY: 12904 AN XY: 74344

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0268

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0702 Hom.: 946

Bravo AF: 0.195

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.47

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: rs3136146; hg19: chr16-14028379;