NM_021922.3:c.-4C>G

Variant names:

• chr6-35452542-C-G
• rs955394922
• NM_021922.3:c.-4C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021922.3(FANCE):​c.-4C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000862 in 1,159,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: FANCE NM_021922.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-4C>G		5_prime_UTR	Exon 1 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.-4C>G		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.-4C>G		5_prime_UTR	Exon 1 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000854656.1		c.-4C>G		5_prime_UTR	Exon 1 of 10	ENSP00000524715.1
	FANCE	ENST00000854658.1		c.-4C>G		5_prime_UTR	Exon 1 of 10	ENSP00000524717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.62e-7 AC: 1 AN: 1159684 Hom.: 0 Cov.: 30 AF XY: 0.00000178 AC XY: 1 AN XY: 561610

African (AFR) AF: 0.0000409 AC: 1 AN: 24470

American (AMR) AF: 0.00 AC: 0 AN: 17216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18142

East Asian (EAS) AF: 0.00 AC: 0 AN: 26906

South Asian (SAS) AF: 0.00 AC: 0 AN: 39798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 958612

Other (OTH) AF: 0.00 AC: 0 AN: 46638

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-1.6
PromoterAI		-0.017	Neutral

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: rs955394922; hg19: chr6-35420319;