Genetic Variant NM_022725.4:c.*2123G>A (chr11-22622563-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022725.4(FANCF):c.*2123G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 178,516 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

FANCF
NM_022725.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.599

Publications

0 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-22622563-C-T is Benign according to our data. Variant chr11-22622563-C-T is described in ClinVar as Benign. ClinVar VariationId is 304172.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00745 (1133/152090) while in subpopulation AFR AF = 0.0258 (1073/41522). AF 95% confidence interval is 0.0246. There are 12 homozygotes in GnomAd4. There are 523 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022725.4. 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
	FANCF	NM_022725.4	MANE Select	c.*2123G>A		3_prime_UTR	Exon 1 of 1	NP_073562.1	A3KME0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCF	ENST00000327470.6	TSL:6 MANE Select	c.*2123G>A		3_prime_UTR	Exon 1 of 1	ENSP00000330875.3	Q9NPI8

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1133

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.00106

AC:

AN:

26426

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

AN XY:

12142

show subpopulations

African (AFR)

AF:

0.0228

AC:

AN:

878

American (AMR)

AF:

0.00180

AC:

AN:

556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1680

East Asian (EAS)

AF:

0.00

AC:

AN:

5508

South Asian (SAS)

AF:

0.00

AC:

AN:

220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.0000656

AC:

AN:

15242

Other (OTH)

AF:

0.00278

AC:

AN:

2162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00745

AC:

1133

AN:

152090

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

523

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0258

AC:

1073

AN:

41522

American (AMR)

AF:

0.00288

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67936

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.00895

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia complementation group F (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.97

(source)

DANN

Benign

0.33

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over