13-102846195-C-T

Variant names:

• chr13-102846195-C-T
• rs2296148
• NM_000123.4:c.-72C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000123.4(ERCC5):​c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,310,150 control chromosomes in the GnomAD database, including 1,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (555 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1279 hom.)
• Consequence: ERCC5 NM_000123.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.40
• Publications: 19 publications found

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]

ENSG00000305730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 13-102846195-C-T is Benign according to our data. Variant chr13-102846195-C-T is described in ClinVar as Benign. ClinVar VariationId is 310910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000123.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	NM_000123.4	MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 15	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.1451-5923C>T		intron	N/A	NP_001191354.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC5	ENST00000652225.2	MANE Select	c.-72C>T		5_prime_UTR	Exon 1 of 15	ENSP00000498881.2
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.1451-5923C>T		intron	N/A	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.764-5923C>T		intron	N/A	ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10817 AN: 152046 Hom.: 551 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0413 AC: 47815 AN: 1157986 Hom.: 1279 Cov.: 16 AF XY: 0.0414 AC XY: 24114 AN XY: 582296

African (AFR) AF: 0.139 AC: 3746 AN: 26976

American (AMR) AF: 0.0280 AC: 1029 AN: 36808

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 938 AN: 23240

East Asian (EAS) AF: 0.0589 AC: 2071 AN: 35180

South Asian (SAS) AF: 0.0480 AC: 3668 AN: 76338

European-Finnish (FIN) AF: 0.0707 AC: 3496 AN: 49414

Middle Eastern (MID) AF: 0.0740 AC: 383 AN: 5174

European-Non Finnish (NFE) AF: 0.0353 AC: 30143 AN: 854912

Other (OTH) AF: 0.0469 AC: 2341 AN: 49944

GnomAD4 genome AF: 0.0713 AC: 10847 AN: 152164 Hom.: 555 Cov.: 32 AF XY: 0.0707 AC XY: 5262 AN XY: 74406

African (AFR) AF: 0.141 AC: 5838 AN: 41482

American (AMR) AF: 0.0362 AC: 554 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5184

South Asian (SAS) AF: 0.0520 AC: 251 AN: 4826

European-Finnish (FIN) AF: 0.0720 AC: 763 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2868 AN: 67988

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0596 Hom.: 163

Bravo AF: 0.0706

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Xeroderma pigmentosum, group G (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.6
DANN	Benign	0.87
PhyloP100		-1.4
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=300/0	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: rs2296148; hg19: chr13-103498545; COSMIC: COSV57279527; COSMIC: COSV57279527;