rs1008512809

Variant names:

• chr6-35452755-G-A
• rs1008512809
• NM_021922.3:c.210G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_021922.3(FANCE):​c.210G>A​(p.Glu70Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,276,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: FANCE NM_021922.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.467
• 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-35452755-G-A is Benign according to our data. Variant chr6-35452755-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 414825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.467 with no splicing effect.

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.210G>A	p.Glu70Glu	synonymous	Exon 1 of 10	NP_068741.1
	FANCE	NM_001410876.1		c.210G>A	p.Glu70Glu	synonymous	Exon 1 of 8	NP_001397805.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.210G>A	p.Glu70Glu	synonymous	Exon 1 of 10	ENSP00000229769.2
	FANCE	ENST00000696264.1		c.210G>A	p.Glu70Glu	synonymous	Exon 1 of 8	ENSP00000512511.1
	FANCE	ENST00000648059.1		n.210G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000497902.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000231 AC: 26 AN: 1124062 Hom.: 0 Cov.: 30 AF XY: 0.0000241 AC XY: 13 AN XY: 539732

African (AFR) AF: 0.00 AC: 0 AN: 23512

American (AMR) AF: 0.00 AC: 0 AN: 10602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15802

East Asian (EAS) AF: 0.00 AC: 0 AN: 26844

South Asian (SAS) AF: 0.00 AC: 0 AN: 34966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3068

European-Non Finnish (NFE) AF: 0.0000277 AC: 26 AN: 940232

Other (OTH) AF: 0.00 AC: 0 AN: 45166

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.58
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.47
PromoterAI		-0.022	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: rs1008512809; hg19: chr6-35420532;