rs50872

Positions:

• chr19-45359191-A-G
• chr19-45359191-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000400.4(ERCC2):​c.1238-1492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 151,800 control chromosomes in the GnomAD database, including 47,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.79 (47799 hom., cov: 29)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.167

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-45359191-A-G is Benign according to our data. Variant chr19-45359191-A-G is described in ClinVar as [Benign]. Clinvar id is 1287693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.1238-1492T>C		intron_variant		ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.1238-1492T>C		intron_variant		1	NM_000400.4	ENSP00000375809.4

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120206 AN: 151682 Hom.: 47761 Cov.: 29

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.793 AC: 120303 AN: 151800 Hom.: 47799 Cov.: 29 AF XY: 0.796 AC XY: 59046 AN XY: 74186

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.792

Alfa AF: 0.783 Hom.: 8213

Bravo AF: 0.796

Asia WGS AF: 0.821 AC: 2857 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs50872; hg19: chr19-45862449;