rs1799797

Variant names:

• chr16-13920136-T-A
• rs1799797
• XR_007064999.1:n.82+6389A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-13920136-T-A
• chr16-13920136-T-C

Variant summary

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

The XR_007064999.1(LOC105371093):​n.82+6389A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,597,848 control chromosomes in the GnomAD database, including 56,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4370 hom., cov: 33)
  • Exomes 𝑓: 0.27 (52273 hom.)
• Consequence: LOC105371093 XR_007064999.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.705
• Publications: 17 publications found

Genes affected

LOC105371093 (HGNC:):

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=-0.79).
• BP6: Variant 16-13920136-T-A is Benign according to our data. Variant chr16-13920136-T-A is described in CliVar as Benign. Clinvar id is 1253478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.-30T>A		upstream_gene_variant		ENST00000311895.8	NP_005227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.-30T>A		upstream_gene_variant		1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35223 AN: 152138 Hom.: 4366 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.240 AC: 56834 AN: 236824 AF XY: 0.246

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.266 AC: 384430 AN: 1445592 Hom.: 52273 Cov.: 32 AF XY: 0.267 AC XY: 192034 AN XY: 719872

African (AFR) AF: 0.172 AC: 5740 AN: 33392

American (AMR) AF: 0.145 AC: 6472 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 7591 AN: 26108

East Asian (EAS) AF: 0.249 AC: 9871 AN: 39670

South Asian (SAS) AF: 0.233 AC: 20076 AN: 86110

European-Finnish (FIN) AF: 0.227 AC: 9340 AN: 41216

Middle Eastern (MID) AF: 0.336 AC: 1810 AN: 5384

European-Non Finnish (NFE) AF: 0.278 AC: 307870 AN: 1108912

Other (OTH) AF: 0.261 AC: 15660 AN: 60100

GnomAD4 genome AF: 0.231 AC: 35244 AN: 152256 Hom.: 4370 Cov.: 33 AF XY: 0.229 AC XY: 17016 AN XY: 74436

African (AFR) AF: 0.173 AC: 7183 AN: 41550

American (AMR) AF: 0.182 AC: 2787 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1357 AN: 5182

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4826

European-Finnish (FIN) AF: 0.229 AC: 2427 AN: 10598

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18474 AN: 68016

Other (OTH) AF: 0.263 AC: 557 AN: 2114

Alfa AF: 0.197 Hom.: 635

Bravo AF: 0.226

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.70
PromoterAI		-0.044	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1799797; hg19: chr16-14013993; COSMIC: COSV61312674;