chr16-13929664-T-C

Variant names:

• chr16-13929664-T-C
• rs3136105
• NM_005236.3:c.793-1046T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005236.3(ERCC4):​c.793-1046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,230 control chromosomes in the GnomAD database, including 1,482 homozygotes. 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: 𝑓 0.11 (1482 hom., cov: 33)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.793-1046T>C		intron_variant	Intron 4 of 10	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.931-1046T>C		intron_variant	Intron 5 of 11		XP_011520726.1
ERCC4	XM_047433774.1	c.3+973T>C		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.793-1046T>C		intron_variant	Intron 4 of 10	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16864 AN: 152112 Hom.: 1478 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.0959

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0951

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16882 AN: 152230 Hom.: 1482 Cov.: 33 AF XY: 0.108 AC XY: 8010 AN XY: 74446

African (AFR) AF: 0.239 AC: 9930 AN: 41510

American (AMR) AF: 0.0855 AC: 1307 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 333 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4830

European-Finnish (FIN) AF: 0.0738 AC: 783 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4072 AN: 68014

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0881 Hom.: 134

Bravo AF: 0.118

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3136105; hg19: chr16-14023521;