rs3136064

Variant names:

• chr16-13923524-C-T
• rs3136064
• NM_005236.3:c.388+1313C>T

Variant summary

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

The NM_005236.3(ERCC4):​c.388+1313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,976 control chromosomes in the GnomAD database, including 8,091 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 0.32 (8091 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 2 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

LOC105371093 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005236.3. 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.388+1313C>T		intron	N/A	NP_005227.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.388+1313C>T		intron	N/A	ENSP00000310520.7
	ERCC4	ENST00000575156.5	TSL:1	c.388+1313C>T		intron	N/A	ENSP00000459933.1
	ERCC4	ENST00000682617.1		c.388+1313C>T		intron	N/A	ENSP00000507912.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49016 AN: 151858 Hom.: 8074 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.323 AC: 49070 AN: 151976 Hom.: 8091 Cov.: 32 AF XY: 0.320 AC XY: 23746 AN XY: 74292

African (AFR) AF: 0.326 AC: 13506 AN: 41444

American (AMR) AF: 0.263 AC: 4009 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5162

South Asian (SAS) AF: 0.272 AC: 1309 AN: 4818

European-Finnish (FIN) AF: 0.310 AC: 3266 AN: 10536

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23105 AN: 67964

Other (OTH) AF: 0.349 AC: 736 AN: 2110

Alfa AF: 0.331 Hom.: 1073

Bravo AF: 0.321

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.54
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs3136064; hg19: chr16-14017381;