16-13950918-GCC-GC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005236.3(ERCC4):c.*2577delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6860 hom., cov: 15)

Exomes 𝑓: 0.30 ( 2114 hom. )

Consequence

ERCC4
NM_005236.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00

Publications

1 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 -16 ACMG points.

BP6

Variant 16-13950918-GC-G is Benign according to our data. Variant chr16-13950918-GC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3 link	c.*2577delC	3_prime_UTR_variant	Exon 11 of 11	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 link	c.*2577delC	3_prime_UTR_variant	Exon 12 of 12		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 link	c.*2577delC	3_prime_UTR_variant	Exon 8 of 8		XP_047289730.1
ERCC4	XM_011522427.2 link	c.*2577delC	3_prime_UTR_variant	Exon 6 of 6		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.*2577delC		3_prime_UTR_variant	Exon 11 of 11	1	NM_005236.3	ENSP00000310520.7		Q92889-1
ERCC4	ENST00000682617.1 link	c.*2577delC		3_prime_UTR_variant	Exon 12 of 12			ENSP00000507912.1		A0A804HKF9

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44569

AN:

151588

Hom.:

6848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.407

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.301

AC:

13214

AN:

43848

Hom.:

2114

Cov.:

AF XY:

0.307

AC XY:

6243

AN XY:

20360

show subpopulations

African (AFR)

AF:

0.212

AC:

380

AN:

1796

American (AMR)

AF:

0.236

AC:

280

AN:

1184

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

991

AN:

2804

East Asian (EAS)

AF:

0.208

AC:

1542

AN:

7430

South Asian (SAS)

AF:

0.226

AC:

AN:

368

European-Finnish (FIN)

AF:

0.316

AC:

AN:

Middle Eastern (MID)

AF:

0.370

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.329

AC:

8663

AN:

26302

Other (OTH)

AF:

0.318

AC:

1166

AN:

3664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

428

856

1283

1711

2139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.294

AC:

44612

AN:

151706

Hom.:

6860

Cov.:

AF XY:

0.292

AC XY:

21617

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.230

AC:

9509

AN:

41360

American (AMR)

AF:

0.252

AC:

3836

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1314

AN:

3466

East Asian (EAS)

AF:

0.239

AC:

1231

AN:

5152

South Asian (SAS)

AF:

0.266

AC:

1280

AN:

4804

European-Finnish (FIN)

AF:

0.308

AC:

3220

AN:

10466

Middle Eastern (MID)

AF:

0.403

AC:

117

AN:

290

European-Non Finnish (NFE)

AF:

0.339

AC:

23029

AN:

67916

Other (OTH)

AF:

0.327

AC:

690

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1606

3212

4819

6425

8031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.314

Hom.:

918

Bravo

AF:

0.289

Asia WGS

AF:

0.293

AC:

1022

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

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

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

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

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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