chr5-60892395-C-T

Variant names:

• chr5-60892395-C-T
• rs4235483
• NM_000082.4:c.844-1309G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000082.4(ERCC8):​c.844-1309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 542,060 control chromosomes in the GnomAD database, including 36,133 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 0.37 (10697 hom., cov: 31)
  • Exomes 𝑓: 0.35 (25436 hom.)
• Consequence: ERCC8 NM_000082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 16 publications found

Genes affected

ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

GNL3LP1 (HGNC:25733): (G protein nucleolar 3 like pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC8	NM_000082.4	MANE Select	c.844-1309G>A		intron	N/A	NP_000073.1
	ERCC8	NM_001007233.3		c.670-1309G>A		intron	N/A	NP_001007234.1
	ERCC8	NM_001290285.2		c.385-1309G>A		intron	N/A	NP_001277214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC8	ENST00000676185.1	MANE Select	c.844-1309G>A		intron	N/A	ENSP00000501614.1
	ERCC8	ENST00000265038.10	TSL:1	c.901-1309G>A		intron	N/A	ENSP00000265038.6
	GNL3LP1	ENST00000399458.2	TSL:6	n.1183G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55784 AN: 151824 Hom.: 10681 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.350 AC: 136398 AN: 390118 Hom.: 25436 Cov.: 0 AF XY: 0.352 AC XY: 77383 AN XY: 220008

African (AFR) AF: 0.377 AC: 4135 AN: 10968

American (AMR) AF: 0.236 AC: 8327 AN: 35292

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 4501 AN: 11020

East Asian (EAS) AF: 0.0538 AC: 869 AN: 16154

South Asian (SAS) AF: 0.327 AC: 20560 AN: 62916

European-Finnish (FIN) AF: 0.377 AC: 11953 AN: 31720

Middle Eastern (MID) AF: 0.432 AC: 1248 AN: 2888

European-Non Finnish (NFE) AF: 0.388 AC: 78086 AN: 201034

Other (OTH) AF: 0.371 AC: 6719 AN: 18126

GnomAD4 genome AF: 0.367 AC: 55831 AN: 151942 Hom.: 10697 Cov.: 31 AF XY: 0.364 AC XY: 27040 AN XY: 74238

African (AFR) AF: 0.385 AC: 15942 AN: 41420

American (AMR) AF: 0.318 AC: 4850 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3472

East Asian (EAS) AF: 0.0570 AC: 295 AN: 5174

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4816

European-Finnish (FIN) AF: 0.363 AC: 3825 AN: 10546

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26772 AN: 67928

Other (OTH) AF: 0.379 AC: 799 AN: 2108

Alfa AF: 0.379 Hom.: 3601

Bravo AF: 0.363

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.9
DANN	Benign	0.51
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4235483; hg19: chr5-60188222; COSMIC: COSV54015135;