16-13921224-G-C

Position:

• chr16-13921224-G-C

Variant summary

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

The NM_005236.3(ERCC4):​c.208-807G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,008 control chromosomes in the GnomAD database, including 4,404 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 0.23 (4404 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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	Protein	UniProt
ERCC4	NM_005236.3	c.208-807G>C		intron_variant		ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.208-807G>C		intron_variant			XP_011520726.1
LOC105371093	XR_007064999.1	n.82+5301C>G		intron_variant
LOC105371093	XR_007065000.1	n.82+5301C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.208-807G>C		intron_variant		1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35336 AN: 151890 Hom.: 4400 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.233 AC: 35357 AN: 152008 Hom.: 4404 Cov.: 32 AF XY: 0.230 AC XY: 17103 AN XY: 74322

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.264

Alfa AF: 0.251 Hom.: 600

Bravo AF: 0.227

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.67

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: rs744154; hg19: chr16-14015081;