rs3136112

Variant names:

• chr16-13930550-C-A
• rs3136112
• NM_005236.3:c.793-160C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-13930550-C-A
• chr16-13930550-C-T

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.793-160C>A variant causes a intron 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 4 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

ENSG00000262732 (HGNC:):

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.793-160C>A		intron_variant	Intron 4 of 10	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.931-160C>A		intron_variant	Intron 5 of 11		XP_011520726.1
ERCC4	XM_047433774.1	c.4-160C>A		intron_variant	Intron 1 of 7		XP_047289730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.793-160C>A		intron_variant	Intron 4 of 10	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 449804 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 238210

African (AFR) AF: 0.00 AC: 0 AN: 12414

American (AMR) AF: 0.00 AC: 0 AN: 17588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14080

East Asian (EAS) AF: 0.00 AC: 0 AN: 30622

South Asian (SAS) AF: 0.00 AC: 0 AN: 40740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 275580

Other (OTH) AF: 0.00 AC: 0 AN: 25916

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.68
DANN	Benign	0.25
PhyloP100		-0.28

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: rs3136112; hg19: chr16-14024407;