16-13930550-C-T

Position:

• chr16-13930550-C-T

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.793-160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 600,984 control chromosomes in the GnomAD database, including 40,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14231 hom., cov: 32)
  • Exomes 𝑓: 0.33 (26131 hom.)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.280

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-13930550-C-T is Benign according to our data. Variant chr16-13930550-C-T is described in ClinVar as [Benign]. Clinvar id is 1288461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.793-160C>T		intron_variant		ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.931-160C>T		intron_variant			XP_011520726.1
ERCC4	XM_047433774.1	c.4-160C>T		intron_variant			XP_047289730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.793-160C>T		intron_variant		1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62186 AN: 151780 Hom.: 14190 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.334 AC: 149949 AN: 449086 Hom.: 26131 AF XY: 0.334 AC XY: 79366 AN XY: 237810

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.410 AC: 62291 AN: 151898 Hom.: 14231 Cov.: 32 AF XY: 0.404 AC XY: 29987 AN XY: 74258

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.411

Alfa AF: 0.378 Hom.: 1461

Bravo AF: 0.424

Asia WGS AF: 0.331 AC: 1151 AN: 3474

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

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.27

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: rs3136112; hg19: chr16-14024407;