16-13938236-T-G

Variant names:

• chr16-13938236-T-G
• rs3136166
• NM_005236.3:c.1904+378T>G

Variant summary

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

The NM_005236.3(ERCC4):​c.1904+378T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,966 control chromosomes in the GnomAD database, including 16,257 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 0.43 (16257 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	NM_005236.3	MANE Select	c.1904+378T>G		intron	N/A	NP_005227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.1904+378T>G		intron	N/A	ENSP00000310520.7
	ERCC4	ENST00000682826.1		n.*1596T>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000507274.1
	ERCC4	ENST00000682909.1		n.4322T>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65988 AN: 151848 Hom.: 16207 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.435 AC: 66104 AN: 151966 Hom.: 16257 Cov.: 32 AF XY: 0.429 AC XY: 31840 AN XY: 74284

African (AFR) AF: 0.678 AC: 28073 AN: 41416

American (AMR) AF: 0.369 AC: 5638 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3464

East Asian (EAS) AF: 0.250 AC: 1293 AN: 5174

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4806

European-Finnish (FIN) AF: 0.309 AC: 3265 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23511 AN: 67972

Other (OTH) AF: 0.436 AC: 919 AN: 2110

Alfa AF: 0.368 Hom.: 17874

Bravo AF: 0.452

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		0.30
Mutation Taster		=99/1	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: rs3136166; hg19: chr16-14032093;