11-22625187-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BS1BS2

The NM_022725.4(FANCF):c.624G>T(p.Ala208Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,610,804 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 31 hom., cov: 33)

Exomes 𝑓: 0.00098 ( 24 hom. )

Consequence

FANCF
NM_022725.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0290

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group F
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 11-22625187-C-A is Benign according to our data. Variant chr11-22625187-C-A is described in ClinVar as [Benign]. Clinvar id is 241442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.029 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00967 (1472/152300) while in subpopulation AFR AF = 0.0338 (1404/41556). AF 95% confidence interval is 0.0323. There are 31 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCF	NM_022725.4 link	c.624G>T	p.Ala208Ala	synonymous_variant	Exon 1 of 1	ENST00000327470.6	NP_073562.1	Q9NPI8A3KME0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCF	ENST00000327470.6 link	c.624G>T	p.Ala208Ala	synonymous_variant	Exon 1 of 1	6	NM_022725.4	ENSP00000330875.3		Q9NPI8

Frequencies

GnomAD3 genomes

AF:

0.00967

AC:

1472

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00265

AC:

658

AN:

248206

AF XY:

0.00198

show subpopulations

Gnomad AFR exome

AF:

0.0371

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000803

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000979

AC:

1428

AN:

1458504

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

624

AN XY:

725300

show subpopulations

African (AFR)

AF:

0.0362

AC:

1206

AN:

33298

American (AMR)

AF:

0.00156

AC:

AN:

44244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25828

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1110186

Other (OTH)

AF:

0.00204

AC:

123

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00967

AC:

1472

AN:

152300

Hom.:

Cov.:

AF XY:

0.00929

AC XY:

692

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0338

AC:

1404

AN:

41556

American (AMR)

AF:

0.00314

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

150

225

300

375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00444

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group F

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

-0.029

PromoterAI

-0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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11-22625187-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over