rs4150275

Positions:

• chr13-102854778-G-A
• chr13-102854778-G-C

Variant summary

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

The NM_000123.4(ERCC5):​c.467+404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,228 control chromosomes in the GnomAD database, including 160 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 0.044 (160 hom., cov: 33)
• Consequence: ERCC5 NM_000123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

ERCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0437 (6650/152228) while in subpopulation SAS AF= 0.0482 (232/4818). AF 95% confidence interval is 0.0432. There are 160 homozygotes in gnomad4. There are 3306 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 160 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC5	NM_000123.4	c.467+404G>A		intron_variant		ENST00000652225.2	NP_000114.3
BIVM-ERCC5	NM_001204425.2	c.1829+404G>A		intron_variant			NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC5	ENST00000652225.2	c.467+404G>A		intron_variant			NM_000123.4	ENSP00000498881.2
BIVM-ERCC5	ENST00000639435.1	c.1829+404G>A		intron_variant		5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.1142+404G>A		intron_variant		5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6642 AN: 152110 Hom.: 161 Cov.: 33

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0437 AC: 6650 AN: 152228 Hom.: 160 Cov.: 33 AF XY: 0.0444 AC XY: 3306 AN XY: 74428

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0299 Hom.: 22

Bravo AF: 0.0395

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.78

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: rs4150275; hg19: chr13-103507128;