16-13930550-C-T

Variant names:

• chr16-13930550-C-T
• rs3136112
• NM_005236.3:c.793-160C>T

Variant summary

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

The NM_005236.3(ERCC4):​c.793-160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 600,984 control chromosomes in the GnomAD database, including 40,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14231 hom., cov: 32)
  • Exomes 𝑓: 0.33 (26131 hom.)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.280
• Publications: 4 publications found

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

ERCC4 Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group F

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, ClinGen
• Fanconi anemia complementation group Q

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• XFE progeroid syndrome

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• Fanconi anemia

  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

ENSG00000262732 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-13930550-C-T is Benign according to our data. Variant chr16-13930550-C-T is described in ClinVar as [Benign]. Clinvar id is 1288461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.793-160C>T		intron_variant	Intron 4 of 10	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.931-160C>T		intron_variant	Intron 5 of 11		XP_011520726.1
ERCC4	XM_047433774.1	c.4-160C>T		intron_variant	Intron 1 of 7		XP_047289730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.793-160C>T		intron_variant	Intron 4 of 10	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62186 AN: 151780 Hom.: 14190 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.334 AC: 149949 AN: 449086 Hom.: 26131 AF XY: 0.334 AC XY: 79366 AN XY: 237810

African (AFR) AF: 0.618 AC: 7657 AN: 12400

American (AMR) AF: 0.341 AC: 5985 AN: 17552

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 5305 AN: 14058

East Asian (EAS) AF: 0.231 AC: 7070 AN: 30582

South Asian (SAS) AF: 0.327 AC: 13297 AN: 40666

European-Finnish (FIN) AF: 0.294 AC: 9058 AN: 30796

Middle Eastern (MID) AF: 0.411 AC: 821 AN: 1998

European-Non Finnish (NFE) AF: 0.333 AC: 91607 AN: 275150

Other (OTH) AF: 0.353 AC: 9149 AN: 25884

GnomAD4 genome AF: 0.410 AC: 62291 AN: 151898 Hom.: 14231 Cov.: 32 AF XY: 0.404 AC XY: 29987 AN XY: 74258

African (AFR) AF: 0.623 AC: 25795 AN: 41424

American (AMR) AF: 0.354 AC: 5404 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1261 AN: 5172

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3109 AN: 10520

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22545 AN: 67916

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.387 Hom.: 1600

Bravo AF: 0.424

Asia WGS AF: 0.331 AC: 1151 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 10, 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	-0.93
CADD	Benign	0.93
DANN	Benign	0.27
PhyloP100		-0.28
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: rs3136112; hg19: chr16-14024407;