16-13936503-C-T

Variant names:

• chr16-13936503-C-T
• rs3136155
• NM_005236.3:c.1811+760C>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.1811+760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,050 control chromosomes in the GnomAD database, including 14,481 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 0.41 (14481 hom., cov: 33)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.1811+760C>T		intron_variant	Intron 8 of 10	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.1949+760C>T		intron_variant	Intron 9 of 11		XP_011520726.1
ERCC4	XM_047433774.1	c.1022+760C>T		intron_variant	Intron 5 of 7		XP_047289730.1
ERCC4	XM_011522427.2	c.461+760C>T		intron_variant	Intron 3 of 5		XP_011520729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.1811+760C>T		intron_variant	Intron 8 of 10	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61970 AN: 151932 Hom.: 14439 Cov.: 33

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.408 AC: 62063 AN: 152050 Hom.: 14481 Cov.: 33 AF XY: 0.400 AC XY: 29693 AN XY: 74312

African (AFR) AF: 0.642 AC: 26651 AN: 41482

American (AMR) AF: 0.299 AC: 4559 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1264 AN: 5180

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4824

European-Finnish (FIN) AF: 0.279 AC: 2943 AN: 10552

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22655 AN: 67968

Other (OTH) AF: 0.399 AC: 841 AN: 2106

Alfa AF: 0.197 Hom.: 373

Bravo AF: 0.422

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-0.23
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: rs3136155; hg19: chr16-14030360;