6-35455712-A-G

Variant names:

• chr6-35455712-A-G
• rs7757405
• NM_021922.3:c.249-35A>G

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.249-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,610,456 control chromosomes in the GnomAD database, including 386,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42370 hom., cov: 31)
  • Exomes 𝑓: 0.69 (344431 hom.)
• Consequence: FANCE NM_021922.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.69
• Publications: 21 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=-0.83).
• BP6: Variant 6-35455712-A-G is Benign according to our data. Variant chr6-35455712-A-G is described in ClinVar as Benign. ClinVar VariationId is 261434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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.249-35A>G		intron	N/A	NP_068741.1
	FANCE	NM_001410876.1		c.249-35A>G		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.249-35A>G		intron	N/A	ENSP00000229769.2
	FANCE	ENST00000696264.1		c.249-35A>G		intron	N/A	ENSP00000512511.1
	FANCE	ENST00000648059.1		n.249-35A>G		intron	N/A	ENSP00000497902.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112591 AN: 151894 Hom.: 42316 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.740

GnomAD2 exomes AF: 0.721 AC: 179596 AN: 249262 AF XY: 0.713

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.682

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.673

Gnomad OTH exome AF: 0.705

GnomAD4 exome AF: 0.685 AC: 999514 AN: 1458444 Hom.: 344431 Cov.: 44 AF XY: 0.686 AC XY: 497693 AN XY: 725636

African (AFR) AF: 0.872 AC: 29161 AN: 33442

American (AMR) AF: 0.814 AC: 36380 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 19117 AN: 26130

East Asian (EAS) AF: 0.707 AC: 28071 AN: 39690

South Asian (SAS) AF: 0.742 AC: 63941 AN: 86176

European-Finnish (FIN) AF: 0.692 AC: 35637 AN: 51470

Middle Eastern (MID) AF: 0.703 AC: 3752 AN: 5334

European-Non Finnish (NFE) AF: 0.667 AC: 741291 AN: 1111198

Other (OTH) AF: 0.699 AC: 42164 AN: 60288

GnomAD4 genome AF: 0.741 AC: 112703 AN: 152012 Hom.: 42370 Cov.: 31 AF XY: 0.742 AC XY: 55088 AN XY: 74288

African (AFR) AF: 0.865 AC: 35928 AN: 41512

American (AMR) AF: 0.765 AC: 11679 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2555 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3525 AN: 5150

South Asian (SAS) AF: 0.743 AC: 3576 AN: 4812

European-Finnish (FIN) AF: 0.696 AC: 7354 AN: 10568

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45766 AN: 67924

Other (OTH) AF: 0.742 AC: 1560 AN: 2102

Alfa AF: 0.698 Hom.: 114642

Bravo AF: 0.754

Asia WGS AF: 0.738 AC: 2565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group E Benign:2

Aug 10, 2021

Genome-Nilou Lab

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 specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jan 10, 2019

GeneDx

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	-0.83
CADD	Benign	8.0
DANN	Benign	0.73
PhyloP100		1.7
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)		0.0		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: rs7757405; hg19: chr6-35423489; COSMIC: COSV57690099;