rs2276466

Variant names:

• chr16-13949318-C-A
• rs2276466
• NM_005236.3:c.*971C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-13949318-C-A
• chr16-13949318-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005236.3(ERCC4):​c.*971C>A 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERCC4 NM_005236.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 43 publications found

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

ACMG classification

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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.*971C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.*971C>A		3_prime_UTR_variant	Exon 12 of 12		XP_011520726.1
ERCC4	XM_047433774.1	c.*971C>A		3_prime_UTR_variant	Exon 8 of 8		XP_047289730.1
ERCC4	XM_011522427.2	c.*971C>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	c.*971C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_005236.3	ENSP00000310520.7
ERCC4	ENST00000683962.1	n.*3416C>A		non_coding_transcript_exon_variant	Exon 12 of 12			ENSP00000506854.1
ERCC4	ENST00000682617.1	c.*971C>A		3_prime_UTR_variant	Exon 12 of 12			ENSP00000507912.1
ERCC4	ENST00000683962.1	n.*3416C>A		3_prime_UTR_variant	Exon 12 of 12			ENSP00000506854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 81622 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 37560

African (AFR) AF: 0.00 AC: 0 AN: 3900

American (AMR) AF: 0.00 AC: 0 AN: 2510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5142

East Asian (EAS) AF: 0.00 AC: 0 AN: 11510

South Asian (SAS) AF: 0.00 AC: 0 AN: 708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50366

Other (OTH) AF: 0.00 AC: 0 AN: 6792

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.74
DANN	Benign	0.62
PhyloP100		-2.1

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

Other links and lift over

dbSNP: rs2276466; hg19: chr16-14043175;