chr11-22623057-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022725.4(FANCF):​c.*1629C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 205,596 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 170 hom., cov: 33)
Exomes 𝑓: 0.029 ( 39 hom. )

Consequence

FANCF
NM_022725.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.278
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=-0.79).
BP6
Variant 11-22623057-G-A is Benign according to our data. Variant chr11-22623057-G-A is described in ClinVar as [Benign]. Clinvar id is 304177.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-22623057-G-A is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FANCFNM_022725.4 linkuse as main transcriptc.*1629C>T 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.*1629C>T 3_prime_UTR_variant 1/1 NM_022725.4 ENSP00000330875 P1

Frequencies

GnomAD3 genomes
AF:
0.0374
AC:
5677
AN:
151948
Hom.:
168
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0783
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0369
Gnomad ASJ
AF:
0.0107
Gnomad EAS
AF:
0.0794
Gnomad SAS
AF:
0.00477
Gnomad FIN
AF:
0.0357
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0143
Gnomad OTH
AF:
0.0250
GnomAD4 exome
AF:
0.0291
AC:
1558
AN:
53530
Hom.:
39
Cov.:
0
AF XY:
0.0278
AC XY:
690
AN XY:
24846
show subpopulations
Gnomad4 AFR exome
AF:
0.0691
Gnomad4 AMR exome
AF:
0.0441
Gnomad4 ASJ exome
AF:
0.00778
Gnomad4 EAS exome
AF:
0.0912
Gnomad4 SAS exome
AF:
0.00644
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0132
Gnomad4 OTH exome
AF:
0.0238
GnomAD4 genome
AF:
0.0375
AC:
5701
AN:
152066
Hom.:
170
Cov.:
33
AF XY:
0.0380
AC XY:
2827
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0785
Gnomad4 AMR
AF:
0.0374
Gnomad4 ASJ
AF:
0.0107
Gnomad4 EAS
AF:
0.0796
Gnomad4 SAS
AF:
0.00456
Gnomad4 FIN
AF:
0.0357
Gnomad4 NFE
AF:
0.0143
Gnomad4 OTH
AF:
0.0247
Alfa
AF:
0.0269
Hom.:
39
Bravo
AF:
0.0400
Asia WGS
AF:
0.0450
AC:
157
AN:
3478

ClinVar

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

Submissions by phenotype

Fanconi anemia complementation group F Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.4
DANN
Benign
0.74

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: rs10500938; hg19: chr11-22644603; API