rs56012340

Variant names:

• chr16-13950924-C-A
• rs56012340
• NM_005236.3:c.*2577C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-13950924-C-A
• chr16-13950924-C-T

Variant summary

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

The NM_005236.3(ERCC4):​c.*2577C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 195,684 control chromosomes in the GnomAD database, including 5,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4462 hom., cov: 32)
  • Exomes 𝑓: 0.26 (1525 hom.)
• Consequence: ERCC4 NM_005236.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.351
• Publications: 2 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: ClinGen, G2P, Genomics England PanelApp
• Fanconi anemia complementation group Q

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-13950924-C-A is Benign according to our data. Variant chr16-13950924-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	NM_005236.3	MANE Select	c.*2577C>A		3_prime_UTR	Exon 11 of 11	NP_005227.1	Q92889-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.*2577C>A		3_prime_UTR	Exon 11 of 11	ENSP00000310520.7	Q92889-1
	ERCC4	ENST00000682617.1		c.*2577C>A		3_prime_UTR	Exon 12 of 12	ENSP00000507912.1	A0A804HKF9

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35470 AN: 151522 Hom.: 4458 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.259 AC: 11416 AN: 44046 Hom.: 1525 Cov.: 0 AF XY: 0.266 AC XY: 5438 AN XY: 20476

African (AFR) AF: 0.152 AC: 273 AN: 1800

American (AMR) AF: 0.191 AC: 225 AN: 1176

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 793 AN: 2780

East Asian (EAS) AF: 0.209 AC: 1561 AN: 7456

South Asian (SAS) AF: 0.214 AC: 80 AN: 374

European-Finnish (FIN) AF: 0.278 AC: 10 AN: 36

Middle Eastern (MID) AF: 0.318 AC: 82 AN: 258

European-Non Finnish (NFE) AF: 0.280 AC: 7415 AN: 26486

Other (OTH) AF: 0.265 AC: 977 AN: 3680

GnomAD4 genome AF: 0.234 AC: 35493 AN: 151638 Hom.: 4462 Cov.: 32 AF XY: 0.231 AC XY: 17135 AN XY: 74074

African (AFR) AF: 0.165 AC: 6801 AN: 41324

American (AMR) AF: 0.187 AC: 2845 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1025 AN: 3456

East Asian (EAS) AF: 0.235 AC: 1212 AN: 5166

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4810

European-Finnish (FIN) AF: 0.234 AC: 2452 AN: 10482

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19037 AN: 67880

Other (OTH) AF: 0.273 AC: 574 AN: 2106

Alfa AF: 0.246 Hom.: 572

Bravo AF: 0.228

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Xeroderma pigmentosum, group F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.59
PhyloP100		-0.35
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: rs56012340; hg19: chr16-14044781; COSMIC: COSV61313340; COSMIC: COSV61313340;