rs4713866

Variant names:

• chr6-35452490-C-T
• rs4713866
• NM_021922.3:c.-56C>T

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.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0095 in 1,225,830 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0092 (135 hom.)
• Consequence: FANCE NM_021922.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.749
• Publications: 6 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.82).
• BP6: Variant 6-35452490-C-T is Benign according to our data. Variant chr6-35452490-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0518 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	NM_021922.3	MANE Select	c.-56C>T		5_prime_UTR	Exon 1 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.-56C>T		5_prime_UTR	Exon 1 of 8	NP_001397805.1	A0A8Q3WL50

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.-56C>T		5_prime_UTR	Exon 1 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000854656.1		c.-56C>T		5_prime_UTR	Exon 1 of 10	ENSP00000524715.1
	FANCE	ENST00000854658.1		c.-56C>T		5_prime_UTR	Exon 1 of 10	ENSP00000524717.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1785 AN: 152182 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00598

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00754

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00919 AC: 9865 AN: 1073532 Hom.: 135 Cov.: 29 AF XY: 0.00929 AC XY: 4735 AN XY: 509584

African (AFR) AF: 0.00644 AC: 144 AN: 22354

American (AMR) AF: 0.0503 AC: 412 AN: 8186

Ashkenazi Jewish (ASJ) AF: 0.00441 AC: 61 AN: 13822

East Asian (EAS) AF: 0.0707 AC: 1827 AN: 25828

South Asian (SAS) AF: 0.0134 AC: 299 AN: 22242

European-Finnish (FIN) AF: 0.00386 AC: 80 AN: 20706

Middle Eastern (MID) AF: 0.0253 AC: 80 AN: 3158

European-Non Finnish (NFE) AF: 0.00704 AC: 6440 AN: 914532

Other (OTH) AF: 0.0122 AC: 522 AN: 42704

GnomAD4 genome AF: 0.0117 AC: 1785 AN: 152298 Hom.: 21 Cov.: 33 AF XY: 0.0131 AC XY: 972 AN XY: 74470

African (AFR) AF: 0.00604 AC: 251 AN: 41586

American (AMR) AF: 0.0354 AC: 542 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.0572 AC: 296 AN: 5178

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4830

European-Finnish (FIN) AF: 0.00528 AC: 56 AN: 10616

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00754 AC: 513 AN: 67998

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.00911 Hom.: 2

Bravo AF: 0.0143

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia complementation group E (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.84
PhyloP100		-0.75
PromoterAI		-0.038	Neutral
Mutation Taster		=300/0	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: rs4713866; hg19: chr6-35420267; COSMIC: COSV57690840; COSMIC: COSV57690840;