ENST00000639435.1:c.1450+5918C>T

Variant names:

• chr13-102845721-C-T
• rs56111250
• ENST00000639435.1:c.1450+5918C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000639435.1(BIVM-ERCC5):​c.1450+5918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 198,080 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (83 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (2 hom.)
• Consequence: BIVM-ERCC5 ENST00000639435.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.60
• Publications: 2 publications found

Genes affected

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:):

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]

ERCC5 Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group G

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• cerebrooculofacioskeletal syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• COFS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• xeroderma pigmentosum-Cockayne syndrome complex

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-102845721-C-T is Benign according to our data. Variant chr13-102845721-C-T is described in ClinVar as [Benign]. Clinvar id is 1264211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM-ERCC5	NM_001204425.2	c.1450+5918C>T		intron_variant	Intron 9 of 22		NP_001191354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIVM-ERCC5	ENST00000639435.1	c.1450+5918C>T		intron_variant	Intron 11 of 24	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.763+5918C>T		intron_variant	Intron 10 of 23	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2557 AN: 152246 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0138

GnomAD4 exome AF: 0.00317 AC: 145 AN: 45716 Hom.: 2 Cov.: 0 AF XY: 0.00253 AC XY: 54 AN XY: 21346

African (AFR) AF: 0.0399 AC: 70 AN: 1756

American (AMR) AF: 0.00518 AC: 7 AN: 1352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2784

East Asian (EAS) AF: 0.00413 AC: 31 AN: 7502

South Asian (SAS) AF: 0.00 AC: 0 AN: 1068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 98

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 10 AN: 27212

Other (OTH) AF: 0.00740 AC: 27 AN: 3650

GnomAD4 genome AF: 0.0168 AC: 2565 AN: 152364 Hom.: 83 Cov.: 33 AF XY: 0.0158 AC XY: 1181 AN XY: 74514

African (AFR) AF: 0.0588 AC: 2443 AN: 41576

American (AMR) AF: 0.00399 AC: 61 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68036

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.00208 Hom.: 2

Bravo AF: 0.0192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 03, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.016
DANN	Benign	0.94
PhyloP100		-4.6
PromoterAI		-0.0067	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs56111250; hg19: chr13-103498071;