rs1799800

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.1905-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,430,286 control chromosomes in the GnomAD database, including 51,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4292 hom., cov: 33)

Exomes 𝑓: 0.27 ( 47307 hom. )

Consequence

ERCC4
NM_005236.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.64

Publications

18 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 16-13944695-G-A is Benign according to our data. Variant chr16-13944695-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3 link	c.1905-28G>A	intron_variant	Intron 9 of 10	ENST00000311895.8	NP_005227.1	Q92889-1A0A1W1GSK9
ERCC4	XM_011522424.4 link	c.2043-28G>A	intron_variant	Intron 10 of 11		XP_011520726.1	A0A804HKF9
ERCC4	XM_047433774.1 link	c.1116-28G>A	intron_variant	Intron 6 of 7		XP_047289730.1
ERCC4	XM_011522427.2 link	c.555-28G>A	intron_variant	Intron 4 of 5		XP_011520729.1	B4DXD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8 link	c.1905-28G>A		intron_variant	Intron 9 of 10	1	NM_005236.3	ENSP00000310520.7		Q92889-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34854

AN:

151938

Hom.:

4289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.240

AC:

60105

AN:

250470

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.267

AC:

340803

AN:

1278230

Hom.:

47307

Cov.:

AF XY:

0.268

AC XY:

173139

AN XY:

645940

show subpopulations

African (AFR)

AF:

0.162

AC:

4852

AN:

29990

American (AMR)

AF:

0.145

AC:

6426

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7304

AN:

24974

East Asian (EAS)

AF:

0.232

AC:

9011

AN:

38874

South Asian (SAS)

AF:

0.252

AC:

20797

AN:

82432

European-Finnish (FIN)

AF:

0.224

AC:

11951

AN:

53286

Middle Eastern (MID)

AF:

0.345

AC:

1863

AN:

5404

European-Non Finnish (NFE)

AF:

0.280

AC:

264395

AN:

944522

Other (OTH)

AF:

0.262

AC:

14204

AN:

54302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12411

24822

37232

49643

62054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8164

16328

24492

32656

40820

<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:

0.229

AC:

34874

AN:

152056

Hom.:

4292

Cov.:

AF XY:

0.227

AC XY:

16851

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.164

AC:

6780

AN:

41468

American (AMR)

AF:

0.182

AC:

2785

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

987

AN:

3464

East Asian (EAS)

AF:

0.243

AC:

1259

AN:

5176

South Asian (SAS)

AF:

0.245

AC:

1179

AN:

4822

European-Finnish (FIN)

AF:

0.229

AC:

2421

AN:

10564

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18542

AN:

67956

Other (OTH)

AF:

0.263

AC:

555

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1393

2786

4178

5571

6964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.263

Hom.:

1026

Bravo

AF:

0.223

Asia WGS

AF:

0.271

AC:

944

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

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

XFE progeroid syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group Q

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Xeroderma pigmentosum, group F

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.28

PhyloP100

-1.6

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