NM_005236.3:c.1904+2986T>C

Variant names:

• chr16-13940844-T-C
• rs3136189
• NM_005236.3:c.1904+2986T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005236.3(ERCC4):​c.1904+2986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,114 control chromosomes in the GnomAD database, including 5,081 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 0.25 (5081 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.1904+2986T>C		intron_variant	Intron 9 of 10	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.2042+2986T>C		intron_variant	Intron 10 of 11		XP_011520726.1
ERCC4	XM_047433774.1	c.1115+2986T>C		intron_variant	Intron 6 of 7		XP_047289730.1
ERCC4	XM_011522427.2	c.554+2986T>C		intron_variant	Intron 4 of 5		XP_011520729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.1904+2986T>C		intron_variant	Intron 9 of 10	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38392 AN: 151996 Hom.: 5072 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.253 AC: 38430 AN: 152114 Hom.: 5081 Cov.: 32 AF XY: 0.251 AC XY: 18644 AN XY: 74372

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.294

Alfa AF: 0.276 Hom.: 6124

Bravo AF: 0.251

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs3136189; hg19: chr16-14034701;