rs4150261

Positions:

• chr13-102851920-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000123.4(ERCC5):​c.89-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 152,176 control chromosomes in the GnomAD database, including 8 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 0.0068 (8 hom., cov: 33)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

ERCC5 (HGNC:3437): (ERCC excision repair 5, endonuclease) This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00679 (1034/152176) while in subpopulation NFE AF= 0.0118 (802/68006). AF 95% confidence interval is 0.0111. There are 8 homozygotes in gnomad4. There are 470 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERCC5	NM_000123.4	c.89-198G>A		intron_variant		ENST00000652225.2
BIVM-ERCC5	NM_001204425.2	c.1451-198G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERCC5	ENST00000652225.2	c.89-198G>A		intron_variant			NM_000123.4	P1

Frequencies

GnomAD3 genomes AF: 0.00680 AC: 1034 AN: 152058 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00331

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00794

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00679 AC: 1034 AN: 152176 Hom.: 8 Cov.: 33 AF XY: 0.00632 AC XY: 470 AN XY: 74382

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00794

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0100 Hom.: 1

Bravo AF: 0.00628

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.52

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: rs4150261; hg19: chr13-103504270;