Variant chr16-13944688-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005236.3(ERCC4):c.1905-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,353,222 control chromosomes in the GnomAD database, including 79,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10291 hom., cov: 33)

Exomes 𝑓: 0.33 ( 69214 hom. )

Consequence

ERCC4
NM_005236.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.482

Variant links:

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 links:

ERCC4 (HGNC:):

ERCC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-13944688-T-C is Benign according to our data. Variant chr16-13944688-T-C is described in ClinVar as [Benign]. Clinvar id is 1255392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ERCC4	NM_005236.3 linkuse as main transcript	c.1905-35T>C	intron_variant	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 linkuse as main transcript	c.2043-35T>C	intron_variant		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 linkuse as main transcript	c.1116-35T>C	intron_variant		XP_047289730.1
ERCC4	XM_011522427.2 linkuse as main transcript	c.555-35T>C	intron_variant		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 linkuse as main transcript	c.1905-35T>C		intron_variant		1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54716

AN:

151916

Hom.:

10256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.317

AC:

79088

AN:

249690

Hom.:

13034

AF XY:

0.317

AC XY:

42799

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.334

AC:

401543

AN:

1201188

Hom.:

69214

Cov.:

AF XY:

0.334

AC XY:

203688

AN XY:

610612

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.360

AC:

54796

AN:

152034

Hom.:

10291

Cov.:

AF XY:

0.356

AC XY:

26435

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.454

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.363

Hom.:

1879

Bravo

AF:

0.364

Asia WGS

AF:

0.308

AC:

1074

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

XFE progeroid syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Fanconi anemia complementation group Q

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Xeroderma pigmentosum, group F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.91

DANN

Benign

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over