16-13933094-G-T

Variant names:

• chr16-13933094-G-T
• rs3136130
• ENST00000575156.5:c.*792G>T

Variant summary

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

The ENST00000575156.5(ERCC4):​c.*792G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 377,386 control chromosomes in the GnomAD database, including 21,664 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 0.37 (11095 hom., cov: 26)
  • Exomes 𝑓: 0.29 (10569 hom.)
• Consequence: ERCC4 ENST00000575156.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 9 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: ClinGen, G2P, Genomics England PanelApp
• Fanconi anemia complementation group Q

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000575156.5. 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.1102+809G>T		intron	N/A	NP_005227.1	Q92889-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000575156.5	TSL:1	c.*792G>T		3_prime_UTR	Exon 6 of 6	ENSP00000459933.1	Q92889-2
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.1102+809G>T		intron	N/A	ENSP00000310520.7	Q92889-1
	ERCC4	ENST00000682617.1		c.1240+809G>T		intron	N/A	ENSP00000507912.1	A0A804HKF9

Frequencies

GnomAD3 genomes AF: 0.372 AC: 55173 AN: 148152 Hom.: 11069 Cov.: 26

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.384

GnomAD2 exomes AF: 0.253 AC: 14805 AN: 58628 AF XY: 0.258

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.292 AC: 66871 AN: 229138 Hom.: 10569 Cov.: 0 AF XY: 0.291 AC XY: 38900 AN XY: 133584

African (AFR) AF: 0.471 AC: 1788 AN: 3798

American (AMR) AF: 0.196 AC: 3193 AN: 16316

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 2750 AN: 7632

East Asian (EAS) AF: 0.187 AC: 1214 AN: 6484

South Asian (SAS) AF: 0.261 AC: 12275 AN: 47050

European-Finnish (FIN) AF: 0.282 AC: 2763 AN: 9794

Middle Eastern (MID) AF: 0.434 AC: 1037 AN: 2392

European-Non Finnish (NFE) AF: 0.308 AC: 38489 AN: 124942

Other (OTH) AF: 0.313 AC: 3362 AN: 10730

GnomAD4 genome AF: 0.373 AC: 55242 AN: 148248 Hom.: 11095 Cov.: 26 AF XY: 0.366 AC XY: 26332 AN XY: 71958

African (AFR) AF: 0.516 AC: 20614 AN: 39938

American (AMR) AF: 0.283 AC: 4186 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1320 AN: 3456

East Asian (EAS) AF: 0.243 AC: 1230 AN: 5056

South Asian (SAS) AF: 0.268 AC: 1253 AN: 4680

European-Finnish (FIN) AF: 0.295 AC: 2829 AN: 9580

Middle Eastern (MID) AF: 0.419 AC: 119 AN: 284

European-Non Finnish (NFE) AF: 0.334 AC: 22516 AN: 67488

Other (OTH) AF: 0.385 AC: 796 AN: 2066

Alfa AF: 0.246 Hom.: 1026

Bravo AF: 0.379

Asia WGS AF: 0.307 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.65
PhyloP100		-1.6
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: rs3136130; hg19: chr16-14026951; COSMIC: COSV61310519; COSMIC: COSV61310519;