chr13-102872412-C-T

Variant names:

• chr13-102872412-C-T
• rs4150360
• NM_000123.4:c.2879+14C>T

Variant summary

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

The NM_001204425.2(BIVM-ERCC5):​c.4241+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,613,166 control chromosomes in the GnomAD database, including 221,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15544 hom., cov: 32)
  • Exomes 𝑓: 0.52 (205807 hom.)
• Consequence: BIVM-ERCC5 NM_001204425.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.309
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-102872412-C-T is Benign according to our data. Variant chr13-102872412-C-T is described in ClinVar as Benign. ClinVar VariationId is 255161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204425.2. 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.2879+14C>T		intron	N/A	NP_000114.3
	BIVM-ERCC5	NM_001204425.2		c.4241+14C>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.2879+14C>T		intron	N/A	ENSP00000498881.2
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.4241+14C>T		intron	N/A	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.3554+14C>T		intron	N/A	ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64655 AN: 151982 Hom.: 15533 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.443 AC: 110813 AN: 249990 AF XY: 0.457

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.521 AC: 760704 AN: 1461066 Hom.: 205807 Cov.: 40 AF XY: 0.520 AC XY: 377970 AN XY: 726780

African (AFR) AF: 0.221 AC: 7397 AN: 33466

American (AMR) AF: 0.263 AC: 11749 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13702 AN: 26120

East Asian (EAS) AF: 0.160 AC: 6341 AN: 39690

South Asian (SAS) AF: 0.445 AC: 38326 AN: 86184

European-Finnish (FIN) AF: 0.543 AC: 29010 AN: 53398

Middle Eastern (MID) AF: 0.433 AC: 2497 AN: 5766

European-Non Finnish (NFE) AF: 0.560 AC: 621925 AN: 1111452

Other (OTH) AF: 0.493 AC: 29757 AN: 60368

GnomAD4 genome AF: 0.425 AC: 64691 AN: 152100 Hom.: 15544 Cov.: 32 AF XY: 0.425 AC XY: 31593 AN XY: 74362

African (AFR) AF: 0.232 AC: 9624 AN: 41498

American (AMR) AF: 0.354 AC: 5407 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.185 AC: 959 AN: 5182

South Asian (SAS) AF: 0.437 AC: 2099 AN: 4806

European-Finnish (FIN) AF: 0.553 AC: 5845 AN: 10564

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37330 AN: 67980

Other (OTH) AF: 0.431 AC: 912 AN: 2114

Alfa AF: 0.458 Hom.: 3930

Bravo AF: 0.400

Asia WGS AF: 0.315 AC: 1100 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Xeroderma pigmentosum, group G (4)
-	-	3	not provided (3)
-	-	1	Cerebrooculofacioskeletal syndrome 3 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		-0.31
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: rs4150360; hg19: chr13-103524762; COSMIC: COSV107450824; COSMIC: COSV107450824;