Genetic Variant ERCC4:c.*792G>C (chr16-13933094-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000575156.5(ERCC4):c.*792G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERCC4
ENST00000575156.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

Publications

9 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: ClinGen, G2P, Genomics England PanelApp
Fanconi anemia complementation group Q
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
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:

ENSG00000262732 (HGNC:):

ENSG00000262732 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000575156.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	NM_005236.3	MANE Select	c.1102+809G>C		intron	N/A	NP_005227.1	Q92889-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERCC4	ENST00000575156.5	TSL:1	c.*792G>C	3_prime_UTR	Exon 6 of 6	ENSP00000459933.1	Q92889-2
ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.1102+809G>C	intron	N/A	ENSP00000310520.7	Q92889-1
ERCC4	ENST00000682617.1		c.1240+809G>C	intron	N/A	ENSP00000507912.1	A0A804HKF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

230874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

134540

African (AFR)

AF:

0.00

AC:

AN:

3830

American (AMR)

AF:

0.00

AC:

AN:

16420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7716

East Asian (EAS)

AF:

0.00

AC:

AN:

6528

South Asian (SAS)

AF:

0.00

AC:

AN:

47338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2396

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

125956

Other (OTH)

AF:

0.00

AC:

AN:

10816

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1026

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.44

(source)

DANN

Benign

0.58

PhyloP100

-1.6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over