rs56012340

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005236.3(ERCC4):c.*2577C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 195,684 control chromosomes in the GnomAD database, including 5,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4462 hom., cov: 32)

Exomes 𝑓: 0.26 ( 1525 hom. )

Consequence

ERCC4
NM_005236.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.351

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group F
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, ClinGen
Fanconi anemia complementation group Q
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
XFE progeroid syndrome
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
xeroderma pigmentosum-Cockayne syndrome complex
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERCC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-13950924-C-A is Benign according to our data. Variant chr16-13950924-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ERCC4	NM_005236.3 link	c.*2577C>A	3_prime_UTR_variant	Exon 11 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4 link	c.*2577C>A	3_prime_UTR_variant	Exon 12 of 12		XP_011520726.1
ERCC4	XM_047433774.1 link	c.*2577C>A	3_prime_UTR_variant	Exon 8 of 8		XP_047289730.1
ERCC4	XM_011522427.2 link	c.*2577C>A	3_prime_UTR_variant	Exon 6 of 6		XP_011520729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.*2577C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_005236.3	ENSP00000310520.7
ERCC4	ENST00000682617.1 link	c.*2577C>A		3_prime_UTR_variant	Exon 12 of 12			ENSP00000507912.1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35470

AN:

151522

Hom.:

4458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.259

AC:

11416

AN:

44046

Hom.:

1525

Cov.:

AF XY:

0.266

AC XY:

5438

AN XY:

20476

show subpopulations

African (AFR)

AF:

0.152

AC:

273

AN:

1800

American (AMR)

AF:

0.191

AC:

225

AN:

1176

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

793

AN:

2780

East Asian (EAS)

AF:

0.209

AC:

1561

AN:

7456

South Asian (SAS)

AF:

0.214

AC:

AN:

374

European-Finnish (FIN)

AF:

0.278

AC:

AN:

Middle Eastern (MID)

AF:

0.318

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.280

AC:

7415

AN:

26486

Other (OTH)

AF:

0.265

AC:

977

AN:

3680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

411

821

1232

1642

2053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.234

AC:

35493

AN:

151638

Hom.:

4462

Cov.:

AF XY:

0.231

AC XY:

17135

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.165

AC:

6801

AN:

41324

American (AMR)

AF:

0.187

AC:

2845

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1025

AN:

3456

East Asian (EAS)

AF:

0.235

AC:

1212

AN:

5166

South Asian (SAS)

AF:

0.245

AC:

1180

AN:

4810

European-Finnish (FIN)

AF:

0.234

AC:

2452

AN:

10482

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.280

AC:

19037

AN:

67880

Other (OTH)

AF:

0.273

AC:

574

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1374

2747

4121

5494

6868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.246

Hom.:

572

Bravo

AF:

0.228

Asia WGS

AF:

0.268

AC:

934

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 11, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Xeroderma pigmentosum, group F

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.64

(source)

DANN

Benign

0.59

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over