16-13950918-GCC-GC

Variant names:

• chr16-13950918-GC-G
• rs61422086
• NM_005236.3:c.*2577delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005236.3(ERCC4):​c.*2577delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6860 hom., cov: 15)
  • Exomes 𝑓: 0.30 (2114 hom.)
• Consequence: ERCC4 NM_005236.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00
• Publications: 1 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, Genomics England PanelApp, G2P
• Fanconi anemia complementation group Q

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, 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 -16 ACMG points.

• BP6: Variant 16-13950918-GC-G is Benign according to our data. Variant chr16-13950918-GC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 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.*2577delC		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.*2577delC		3_prime_UTR	Exon 11 of 11	ENSP00000310520.7	Q92889-1
	ERCC4	ENST00000682617.1		c.*2577delC		3_prime_UTR	Exon 12 of 12	ENSP00000507912.1	A0A804HKF9

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44569 AN: 151588 Hom.: 6848 Cov.: 15

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.301 AC: 13214 AN: 43848 Hom.: 2114 Cov.: 0 AF XY: 0.307 AC XY: 6243 AN XY: 20360

African (AFR) AF: 0.212 AC: 380 AN: 1796

American (AMR) AF: 0.236 AC: 280 AN: 1184

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 991 AN: 2804

East Asian (EAS) AF: 0.208 AC: 1542 AN: 7430

South Asian (SAS) AF: 0.226 AC: 83 AN: 368

European-Finnish (FIN) AF: 0.316 AC: 12 AN: 38

Middle Eastern (MID) AF: 0.370 AC: 97 AN: 262

European-Non Finnish (NFE) AF: 0.329 AC: 8663 AN: 26302

Other (OTH) AF: 0.318 AC: 1166 AN: 3664

GnomAD4 genome AF: 0.294 AC: 44612 AN: 151706 Hom.: 6860 Cov.: 15 AF XY: 0.292 AC XY: 21617 AN XY: 74100

African (AFR) AF: 0.230 AC: 9509 AN: 41360

American (AMR) AF: 0.252 AC: 3836 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3466

East Asian (EAS) AF: 0.239 AC: 1231 AN: 5152

South Asian (SAS) AF: 0.266 AC: 1280 AN: 4804

European-Finnish (FIN) AF: 0.308 AC: 3220 AN: 10466

Middle Eastern (MID) AF: 0.403 AC: 117 AN: 290

European-Non Finnish (NFE) AF: 0.339 AC: 23029 AN: 67916

Other (OTH) AF: 0.327 AC: 690 AN: 2110

Alfa AF: 0.314 Hom.: 918

Bravo AF: 0.289

Asia WGS AF: 0.293 AC: 1022 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Xeroderma pigmentosum (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs61422086;

hg19: chr16-14044775;

COSMIC: COSV61311657;

COSMIC: COSV61311657;