rs2276465

Variant names:

• chr16-13949157-G-A
• rs2276465
• NM_005236.3:c.*810G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-13949157-G-A
• chr16-13949157-G-C

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.*810G>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 0.304 in 232,858 control chromosomes in the GnomAD database, including 11,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6930 hom., cov: 32)
  • Exomes 𝑓: 0.32 (4248 hom.)
• Consequence: ERCC4 NM_005236.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.46
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 16-13949157-G-A is Benign according to our data. Variant chr16-13949157-G-A is described in ClinVar as Benign. ClinVar VariationId is 317837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 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.*810G>A		3_prime_UTR	Exon 11 of 11	NP_005227.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC4	ENST00000311895.8	TSL:1 MANE Select	c.*810G>A		3_prime_UTR	Exon 11 of 11	ENSP00000310520.7
	ERCC4	ENST00000682617.1		c.*810G>A		3_prime_UTR	Exon 12 of 12	ENSP00000507912.1
	ERCC4	ENST00000683962.1		n.*3255G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000506854.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44765 AN: 151968 Hom.: 6917 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.321 AC: 25965 AN: 80772 Hom.: 4248 Cov.: 0 AF XY: 0.326 AC XY: 12109 AN XY: 37120

African (AFR) AF: 0.227 AC: 883 AN: 3888

American (AMR) AF: 0.252 AC: 630 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1960 AN: 5104

East Asian (EAS) AF: 0.231 AC: 2629 AN: 11370

South Asian (SAS) AF: 0.259 AC: 181 AN: 700

European-Finnish (FIN) AF: 0.350 AC: 21 AN: 60

Middle Eastern (MID) AF: 0.386 AC: 190 AN: 492

European-Non Finnish (NFE) AF: 0.345 AC: 17238 AN: 49906

Other (OTH) AF: 0.331 AC: 2233 AN: 6756

GnomAD4 genome AF: 0.295 AC: 44805 AN: 152086 Hom.: 6930 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74354

African (AFR) AF: 0.231 AC: 9571 AN: 41466

American (AMR) AF: 0.252 AC: 3845 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1249 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1281 AN: 4828

European-Finnish (FIN) AF: 0.309 AC: 3265 AN: 10576

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23084 AN: 67990

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.286 Hom.: 2530

Bravo AF: 0.289

Asia WGS AF: 0.290 AC: 1011 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.0040
DANN	Benign	0.46
PhyloP100		-4.5
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: rs2276465; hg19: chr16-14043014;