rs3136064

chr16-13923524-C-T

Variant summary

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

The NM_005236.3(ERCC4):c.388+1313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,976 control chromosomes in the GnomAD database, including 8,091 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 0.32 (8091 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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]

LOC105371093 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.388+1313C>T		intron_variant		ENST00000311895.8
LOC105371093	XR_007065000.1	n.82+3001G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.388+1313C>T		intron_variant		1	NM_005236.3	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49016 AN: 151858 Hom.: 8074 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.323 AC: 49070 AN: 151976 Hom.: 8091 Cov.: 32 AF XY: 0.320 AC XY: 23746 AN XY: 74292

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.349

Alfa AF: 0.331 Hom.: 1035

Bravo AF: 0.321

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.53
Dann	Benign	0.54

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: rs3136064; hg19: chr16-14017381;