chr11-22623202-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022725.4(FANCF):​c.*1484G>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 0.00832 in 213,688 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0090 ( 3 hom. )

Consequence

FANCF
NM_022725.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.109
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 11-22623202-C-T is Benign according to our data. Variant chr11-22623202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 877849.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00806 (1227/152276) while in subpopulation NFE AF= 0.013 (887/68014). AF 95% confidence interval is 0.0123. There are 5 homozygotes in gnomad4. There are 566 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FANCFNM_022725.4 linkuse as main transcriptc.*1484G>A 3_prime_UTR_variant 1/1 ENST00000327470.6 NP_073562.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FANCFENST00000327470.6 linkuse as main transcriptc.*1484G>A 3_prime_UTR_variant 1/1 NM_022725.4 ENSP00000330875 P1

Frequencies

GnomAD3 genomes
AF:
0.00806
AC:
1227
AN:
152158
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.00490
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0137
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0130
Gnomad OTH
AF:
0.00478
GnomAD4 exome
AF:
0.00897
AC:
551
AN:
61412
Hom.:
3
Cov.:
0
AF XY:
0.00907
AC XY:
258
AN XY:
28446
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.00385
Gnomad4 ASJ exome
AF:
0.00608
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0238
Gnomad4 NFE exome
AF:
0.0125
Gnomad4 OTH exome
AF:
0.00876
GnomAD4 genome
AF:
0.00806
AC:
1227
AN:
152276
Hom.:
5
Cov.:
33
AF XY:
0.00760
AC XY:
566
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00265
Gnomad4 AMR
AF:
0.00372
Gnomad4 ASJ
AF:
0.00490
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0137
Gnomad4 NFE
AF:
0.0130
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.0110
Hom.:
1
Bravo
AF:
0.00750
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Fanconi anemia complementation group F Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.93
DANN
Benign
0.23

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

LitVar

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

Other links and lift over

dbSNP: rs181285048; hg19: chr11-22644748; API