rs115195341

Variant names:

• chr6-35466306-G-A
• rs115195341
• NM_021922.3:c.1572G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35466306-G-A
• chr6-35466306-G-C
• chr6-35466306-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021922.3(FANCE):​c.1572G>A​(p.Arg524Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0064 in 1,613,944 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (45 hom.)
• Consequence: FANCE NM_021922.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 4.03
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), 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=-0.49).
• BP6: Variant 6-35466306-G-A is Benign according to our data. Variant chr6-35466306-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 221002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0042 (639/152300) while in subpopulation NFE AF = 0.00717 (488/68028). AF 95% confidence interval is 0.00665. There are 1 homozygotes in GnomAd4. There are 285 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 45 AR gene

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.1572G>A	p.Arg524Arg	synonymous	Exon 10 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.*23G>A		3_prime_UTR	Exon 8 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.1572G>A	p.Arg524Arg	synonymous	Exon 10 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000854656.1		c.1575G>A	p.Arg525Arg	synonymous	Exon 10 of 10	ENSP00000524715.1
	FANCE	ENST00000854658.1		c.1551G>A	p.Arg517Arg	synonymous	Exon 10 of 10	ENSP00000524717.1

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 639 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00624

GnomAD2 exomes AF: 0.00411 AC: 1033 AN: 251484 AF XY: 0.00407

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00226

Gnomad NFE exome AF: 0.00645

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00663 AC: 9698 AN: 1461644 Hom.: 45 Cov.: 30 AF XY: 0.00649 AC XY: 4718 AN XY: 727148

African (AFR) AF: 0.00102 AC: 34 AN: 33476

American (AMR) AF: 0.00340 AC: 152 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 98 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.000962 AC: 83 AN: 86250

European-Finnish (FIN) AF: 0.00180 AC: 96 AN: 53412

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.00797 AC: 8865 AN: 1111794

Other (OTH) AF: 0.00580 AC: 350 AN: 60388

GnomAD4 genome AF: 0.00420 AC: 639 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00383 AC XY: 285 AN XY: 74466

African (AFR) AF: 0.00132 AC: 55 AN: 41560

American (AMR) AF: 0.00294 AC: 45 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00717 AC: 488 AN: 68028

Other (OTH) AF: 0.00617 AC: 13 AN: 2106

Alfa AF: 0.00539 Hom.: 3

Bravo AF: 0.00450

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00638

EpiControl AF: 0.00747

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Fanconi anemia complementation group E (4)
-	-	3	not provided (3)
-	-	1	Fanconi anemia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.7
DANN	Benign	0.58
PhyloP100		4.0
Mutation Taster		=100/0	polymorphism

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: rs115195341; hg19: chr6-35434083; COSMIC: COSV104566708;