rs3740615

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022725.4(FANCF):c.-10C>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 0.174 in 1,613,436 control chromosomes in the GnomAD database, including 26,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2058 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24481 hom. )

Consequence

FANCF
NM_022725.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.17

Variant links:

Genes affected

FANCF (HGNC:3587): (FA complementation group F) 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 F. [provided by RefSeq, Jul 2008]

FANCF links:

GAS2 (HGNC:4167): (growth arrest specific 2) The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

GAS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 11-22625820-G-A is Benign according to our data. Variant chr11-22625820-G-A is described in ClinVar as [Benign]. Clinvar id is 261630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22625820-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCF	NM_022725.4 linkuse as main transcript	c.-10C>T		5_prime_UTR_variant	1/1	ENST00000327470.6	NP_073562.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
FANCF	ENST00000327470.6 linkuse as main transcript	c.-10C>T	5_prime_UTR_variant	1/1		NM_022725.4	ENSP00000330875	P1
GAS2	ENST00000528582.5 linkuse as main transcript	c.-21+7G>A	splice_region_variant, intron_variant		3		ENSP00000432584
GAS2	ENST00000648096.1 linkuse as main transcript	n.312G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22573

AN:

152020

Hom.:

2057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.158

AC:

39234

AN:

248564

Hom.:

3733

AF XY:

0.159

AC XY:

21386

AN XY:

134838

show subpopulations

Gnomad AFR exome

AF:

0.0605

Gnomad AMR exome

AF:

0.0758

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.0668

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.177

AC:

257950

AN:

1461298

Hom.:

24481

Cov.:

AF XY:

0.174

AC XY:

126318

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.0561

Gnomad4 AMR exome

AF:

0.0789

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.0699

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.148

AC:

22580

AN:

152138

Hom.:

2058

Cov.:

AF XY:

0.151

AC XY:

11233

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0610

Gnomad4 AMR

AF:

0.0978

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.0665

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.167

Hom.:

4185

Bravo

AF:

0.132

Asia WGS

AF:

0.140

AC:

488

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group F

Benign:3

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0070

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over