6-35459779-G-A

Variant names:

• chr6-35459779-G-A
• rs6457823
• NM_021922.3:c.1316+19G>A

Variant summary

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

The NM_021922.3(FANCE):​c.1316+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 1,609,688 control chromosomes in the GnomAD database, including 8,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2924 hom., cov: 31)
  • Exomes 𝑓: 0.067 (5876 hom.)
• Consequence: FANCE NM_021922.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -4.73
• Publications: 10 publications found

Genes affected

FANCE (HGNC:3586): (FA complementation group E) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group E. [provided by RefSeq, Jul 2008]

FANCE Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group E

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Fanconi anemia

  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=-0.9).
• BP6: Variant 6-35459779-G-A is Benign according to our data. Variant chr6-35459779-G-A is described in ClinVar as Benign. ClinVar VariationId is 261433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	NM_021922.3	MANE Select	c.1316+19G>A		intron	N/A	NP_068741.1
	FANCE	NM_001410876.1		c.1316+19G>A		intron	N/A	NP_001397805.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.1316+19G>A		intron	N/A	ENSP00000229769.2
	FANCE	ENST00000696264.1		c.1316+19G>A		intron	N/A	ENSP00000512511.1
	FANCE	ENST00000648059.1		n.1316+19G>A		intron	N/A	ENSP00000497902.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21822 AN: 151996 Hom.: 2913 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.0905 AC: 22746 AN: 251320 AF XY: 0.0893

Gnomad AFR exome AF: 0.367

Gnomad AMR exome AF: 0.0512

Gnomad ASJ exome AF: 0.0669

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0538

Gnomad OTH exome AF: 0.0705

GnomAD4 exome AF: 0.0675 AC: 98361 AN: 1457574 Hom.: 5876 Cov.: 30 AF XY: 0.0693 AC XY: 50244 AN XY: 725396

African (AFR) AF: 0.379 AC: 12638 AN: 33356

American (AMR) AF: 0.0552 AC: 2469 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 1732 AN: 26110

East Asian (EAS) AF: 0.0832 AC: 3303 AN: 39680

South Asian (SAS) AF: 0.161 AC: 13838 AN: 86160

European-Finnish (FIN) AF: 0.0371 AC: 1981 AN: 53408

Middle Eastern (MID) AF: 0.0799 AC: 460 AN: 5760

European-Non Finnish (NFE) AF: 0.0511 AC: 56644 AN: 1108132

Other (OTH) AF: 0.0879 AC: 5296 AN: 60254

GnomAD4 genome AF: 0.144 AC: 21861 AN: 152114 Hom.: 2924 Cov.: 31 AF XY: 0.142 AC XY: 10570 AN XY: 74374

African (AFR) AF: 0.358 AC: 14812 AN: 41418

American (AMR) AF: 0.0735 AC: 1123 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3472

East Asian (EAS) AF: 0.114 AC: 591 AN: 5176

South Asian (SAS) AF: 0.167 AC: 807 AN: 4826

European-Finnish (FIN) AF: 0.0334 AC: 354 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3610 AN: 68010

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.106 Hom.: 354

Bravo AF: 0.156

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group E Benign:3

Nov 06, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Uncertain:1 Benign:1

Feb 28, 2020

Leiden Open Variation Database

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0040
DANN	Benign	0.51
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6457823; hg19: chr6-35427556; COSMIC: COSV57690059;