rs3743538

Variant names:

• chr16-13948831-G-T
• rs3743538
• NM_005236.3:c.*484G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-13948831-G-T
• chr16-13948831-G-A

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.*484G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 232,326 control chromosomes in the GnomAD database, including 15,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10412 hom., cov: 31)
  • Exomes 𝑓: 0.34 (4699 hom.)
• Consequence: ERCC4 NM_005236.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.84
• Publications: 12 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=-1.01).
• BP6: Variant 16-13948831-G-T is Benign according to our data. Variant chr16-13948831-G-T is described in ClinVar as Benign. ClinVar VariationId is 317830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 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.*484G>T		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.*484G>T		3_prime_UTR	Exon 11 of 11	ENSP00000310520.7	Q92889-1
	ERCC4	ENST00000682617.1		c.*484G>T		3_prime_UTR	Exon 12 of 12	ENSP00000507912.1	A0A804HKF9
	ERCC4	ENST00000683962.1		n.*2929G>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000506854.1	A0A804HI16

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55305 AN: 151730 Hom.: 10381 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.339 AC: 27278 AN: 80478 Hom.: 4699 Cov.: 0 AF XY: 0.341 AC XY: 12633 AN XY: 37022

African (AFR) AF: 0.433 AC: 1673 AN: 3864

American (AMR) AF: 0.355 AC: 878 AN: 2474

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1957 AN: 5080

East Asian (EAS) AF: 0.230 AC: 2609 AN: 11320

South Asian (SAS) AF: 0.308 AC: 221 AN: 718

European-Finnish (FIN) AF: 0.333 AC: 20 AN: 60

Middle Eastern (MID) AF: 0.403 AC: 196 AN: 486

European-Non Finnish (NFE) AF: 0.348 AC: 17305 AN: 49770

Other (OTH) AF: 0.361 AC: 2419 AN: 6706

GnomAD4 genome AF: 0.365 AC: 55401 AN: 151848 Hom.: 10412 Cov.: 31 AF XY: 0.362 AC XY: 26853 AN XY: 74186

African (AFR) AF: 0.442 AC: 18309 AN: 41430

American (AMR) AF: 0.338 AC: 5171 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3460

East Asian (EAS) AF: 0.242 AC: 1235 AN: 5098

South Asian (SAS) AF: 0.314 AC: 1510 AN: 4804

European-Finnish (FIN) AF: 0.309 AC: 3255 AN: 10540

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23283 AN: 67912

Other (OTH) AF: 0.380 AC: 804 AN: 2114

Alfa AF: 0.358 Hom.: 3887

Bravo AF: 0.371

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.63
PhyloP100		-1.8
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: rs3743538; hg19: chr16-14042688; COSMIC: COSV61313346; COSMIC: COSV61313346;