16-13920136-T-A

Position:

• chr16-13920136-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.263 in 1,597,848 control chromosomes in the GnomAD database, including 56,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4370 hom., cov: 33)
  • Exomes 𝑓: 0.27 (52273 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.705

Genes affected

(HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-13920136-T-A is Benign according to our data. Variant chr16-13920136-T-A is described in ClinVar as [Benign]. Clinvar id is 1253478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.-30T>A		upstream_gene_variant		ENST00000311895.8	NP_005227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.-30T>A		upstream_gene_variant		1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35223 AN: 152138 Hom.: 4366 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.240 AC: 56834 AN: 236824 Hom.: 7233 AF XY: 0.246 AC XY: 32033 AN XY: 130188

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.266 AC: 384430 AN: 1445592 Hom.: 52273 Cov.: 32 AF XY: 0.267 AC XY: 192034 AN XY: 719872

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.231 AC: 35244 AN: 152256 Hom.: 4370 Cov.: 33 AF XY: 0.229 AC XY: 17016 AN XY: 74436

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.263

Alfa AF: 0.197 Hom.: 635

Bravo AF: 0.226

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.79
CADD	Benign	2.4
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1799797; hg19: chr16-14013993; COSMIC: COSV61312674;