rs3136202

chr16-13944317-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005236.3(ERCC4):c.1905-406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,760 control chromosomes in the GnomAD database, including 14,525 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 0.41 (14525 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.1905-406G>A		intron_variant		ENST00000311895.8
ERCC4	XM_011522424.4	c.2043-406G>A		intron_variant
ERCC4	XM_011522427.2	c.555-406G>A		intron_variant
ERCC4	XM_047433774.1	c.1116-406G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.1905-406G>A		intron_variant		1	NM_005236.3	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62493 AN: 151642 Hom.: 14483 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 62588 AN: 151760 Hom.: 14525 Cov.: 32 AF XY: 0.406 AC XY: 30078 AN XY: 74148

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.412

Alfa AF: 0.352 Hom.: 14986

Bravo AF: 0.423

Asia WGS AF: 0.320 AC: 1114 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.17
Dann	Benign	0.45

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: rs3136202; hg19: chr16-14038174;