19-45362432-C-T

Position:

• chr19-45362432-C-T

Variant summary

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

The NM_000400.4(ERCC2):​c.1119-790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,094 control chromosomes in the GnomAD database, including 32,072 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 0.63 (32072 hom., cov: 33)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ERCC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.1119-790G>A		intron_variant		ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.1119-790G>A		intron_variant		1	NM_000400.4	ENSP00000375809.4

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96141 AN: 151976 Hom.: 32025 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.633 AC: 96239 AN: 152094 Hom.: 32072 Cov.: 33 AF XY: 0.629 AC XY: 46753 AN XY: 74316

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.589

Alfa AF: 0.522 Hom.: 4157

Bravo AF: 0.640

Asia WGS AF: 0.562 AC: 1955 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.039
DANN	Benign	0.49
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs238404; hg19: chr19-45865690;