19-45353791-T-C

Position:

• chr19-45353791-T-C

Variant summary

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

The NM_000400.4(ERCC2):​c.1666-457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,094 control chromosomes in the GnomAD database, including 39,139 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 0.71 (39139 hom., cov: 32)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC2	NM_000400.4	c.1666-457A>G		intron_variant		ENST00000391945.10
ERCC2	XM_011526611.3	c.1588-457A>G		intron_variant
ERCC2	XR_001753633.3	n.1699-457A>G		intron_variant, non_coding_transcript_variant
ERCC2	XR_007066680.1	n.1621-457A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC2	ENST00000391945.10	c.1666-457A>G		intron_variant		1	NM_000400.4	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107208 AN: 151976 Hom.: 39074 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.706 AC: 107329 AN: 152094 Hom.: 39139 Cov.: 32 AF XY: 0.700 AC XY: 52034 AN XY: 74324

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.638

Alfa AF: 0.652 Hom.: 50131

Bravo AF: 0.707

Asia WGS AF: 0.566 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.98
DANN	Benign	0.87

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: rs238416; hg19: chr19-45857049;