rs50871

Variant names:

• chr19-45359257-C-A
• rs50871
• NM_000400.4:c.1238-1558G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45359257-C-A
• chr19-45359257-C-G

Variant summary

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

The NM_000400.4(ERCC2):​c.1238-1558G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,878 control chromosomes in the GnomAD database, including 33,022 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 0.64 (33022 hom., cov: 31)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.1238-1558G>T		intron_variant	Intron 12 of 22	ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.1238-1558G>T		intron_variant	Intron 12 of 22	1	NM_000400.4	ENSP00000375809.4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96967 AN: 151760 Hom.: 32975 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.639 AC: 97074 AN: 151878 Hom.: 33022 Cov.: 31 AF XY: 0.642 AC XY: 47636 AN XY: 74186

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.599

Alfa AF: 0.537 Hom.: 32322

Bravo AF: 0.648

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99

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: rs50871; hg19: chr19-45862515;