rs3136152

Variant names:

• chr16-13935977-G-A
• rs3136152
• NM_005236.3:c.1811+234G>A

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.1811+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,140 control chromosomes in the GnomAD database, including 2,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (2569 hom., cov: 32)
• Consequence: ERCC4 NM_005236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-13935977-G-A is Benign according to our data. Variant chr16-13935977-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	NM_005236.3	MANE Select	c.1811+234G>A		intron	N/A	NP_005227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.1811+234G>A		intron	N/A	ENSP00000310520.7
	ERCC4	ENST00000682568.1		n.2123G>A		non_coding_transcript_exon	Exon 9 of 9
	ERCC4	ENST00000683407.1		n.2053G>A		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15213 AN: 152022 Hom.: 2561 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0766

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

GnomAD4 genome AF: 0.100 AC: 15257 AN: 152140 Hom.: 2569 Cov.: 32 AF XY: 0.0959 AC XY: 7137 AN XY: 74398

African (AFR) AF: 0.344 AC: 14235 AN: 41420

American (AMR) AF: 0.0419 AC: 641 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00238 AC: 162 AN: 68024

Other (OTH) AF: 0.0758 AC: 160 AN: 2112

Alfa AF: 0.0363 Hom.: 914

Bravo AF: 0.115

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.76
PhyloP100		-0.49
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: rs3136152; hg19: chr16-14029834; COSMIC: COSV61312821; COSMIC: COSV61312821;