rs3136215

Positions:

• chr16-13946425-T-C

Variant summary

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

The NM_005236.3(ERCC4):​c.2018-1189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 152,292 control chromosomes in the GnomAD database, including 151 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 0.035 (151 hom., cov: 33)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.2018-1189T>C		intron_variant		ENST00000311895.8
ERCC4	XM_011522424.4	c.2156-1189T>C		intron_variant
ERCC4	XM_011522427.2	c.668-1189T>C		intron_variant
ERCC4	XM_047433774.1	c.1229-1189T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.2018-1189T>C		intron_variant		1	NM_005236.3	P1

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5397 AN: 152174 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.00917

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0354 AC: 5395 AN: 152292 Hom.: 151 Cov.: 33 AF XY: 0.0324 AC XY: 2411 AN XY: 74476

Gnomad4 AFR AF: 0.00914

Gnomad4 AMR AF: 0.0333

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0437 Hom.: 17

Bravo AF: 0.0353

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3136215; hg19: chr16-14040282;