Genetic Variant FANCF:c.*1338dupA (chr11-22623347-A-AT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_022725.4(FANCF):c.*1338dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.96 ( 70353 hom., cov: 0)

Exomes 𝑓: 0.98 ( 22106 hom. )

Consequence

FANCF
NM_022725.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.574

Publications

3 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCF	NM_022725.4 link	c.*1338dupA		3_prime_UTR_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.*1338dupA		3_prime_UTR_variant	Exon 1 of 1	6	NM_022725.4	ENSP00000330875.3		Q9NPI8

Frequencies

GnomAD3 genomes

AF:

0.961

AC:

146006

AN:

151896

Hom.:

70322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.965

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

0.925

Gnomad SAS

AF:

0.996

Gnomad FIN

AF:

0.980

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.971

GnomAD4 exome

AF:

0.975

AC:

45264

AN:

46424

Hom.:

22106

Cov.:

AF XY:

0.977

AC XY:

20850

AN XY:

21348

show subpopulations

African (AFR)

AF:

0.891

AC:

1760

AN:

1976

American (AMR)

AF:

0.945

AC:

1211

AN:

1282

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

2985

AN:

2988

East Asian (EAS)

AF:

0.902

AC:

6794

AN:

7532

South Asian (SAS)

AF:

0.991

AC:

418

AN:

422

European-Finnish (FIN)

AF:

0.967

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

280

AN:

280

European-Non Finnish (NFE)

AF:

0.998

AC:

27925

AN:

27970

Other (OTH)

AF:

0.979

AC:

3862

AN:

3944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.961

AC:

146093

AN:

152010

Hom.:

70353

Cov.:

AF XY:

0.961

AC XY:

71409

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.889

AC:

36833

AN:

41438

American (AMR)

AF:

0.965

AC:

14726

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3460

AN:

3472

East Asian (EAS)

AF:

0.925

AC:

4730

AN:

5112

South Asian (SAS)

AF:

0.996

AC:

4797

AN:

4816

European-Finnish (FIN)

AF:

0.980

AC:

10369

AN:

10586

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67928

AN:

68010

Other (OTH)

AF:

0.971

AC:

2049

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

278

555

833

1110

1388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.991

Hom.:

2232

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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11-22623347-A-AT

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