rs3136152

chr16-13935977-G-A

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.1811+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,140 control chromosomes in the GnomAD database, including 2,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (2569 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-13935977-G-A is Benign according to our data. Variant chr16-13935977-G-A is described in ClinVar as [Benign]. Clinvar id is 1274439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC4	NM_005236.3	c.1811+234G>A		intron_variant		ENST00000311895.8
ERCC4	XM_011522424.4	c.1949+234G>A		intron_variant
ERCC4	XM_011522427.2	c.461+234G>A		intron_variant
ERCC4	XM_047433774.1	c.1022+234G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC4	ENST00000311895.8	c.1811+234G>A		intron_variant		1	NM_005236.3	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15213 AN: 152022 Hom.: 2561 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0766

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

GnomAD4 genome AF: 0.100 AC: 15257 AN: 152140 Hom.: 2569 Cov.: 32 AF XY: 0.0959 AC XY: 7137 AN XY: 74398

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00238

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0218 Hom.: 403

Bravo AF: 0.115

Asia WGS AF: 0.0200 AC: 69 AN: 3478

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

Mar 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.76

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: rs3136152; hg19: chr16-14029834; COSMIC: COSV61312821; COSMIC: COSV61312821;