15-89260812-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001113378.2(FANCI):​c.257C>T​(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,612,532 control chromosomes in the GnomAD database, including 112,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8212 hom., cov: 32)
Exomes 𝑓: 0.37 ( 103813 hom. )

Consequence

FANCI
NM_001113378.2 missense

Scores

3
15

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.06
Variant links:
Genes affected
FANCI (HGNC:25568): (FA complementation group I) 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 I. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 15-89260812-C-T is Benign according to our data. Variant chr15-89260812-C-T is described in ClinVar as [Benign]. Clinvar id is 257484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FANCINM_001113378.2 linkuse as main transcriptc.257C>T p.Ala86Val missense_variant 4/38 ENST00000310775.12 NP_001106849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FANCIENST00000310775.12 linkuse as main transcriptc.257C>T p.Ala86Val missense_variant 4/381 NM_001113378.2 ENSP00000310842 P1Q9NVI1-3

Frequencies

GnomAD3 genomes
AF:
0.299
AC:
45344
AN:
151798
Hom.:
8212
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0881
Gnomad AMI
AF:
0.391
Gnomad AMR
AF:
0.309
Gnomad ASJ
AF:
0.369
Gnomad EAS
AF:
0.317
Gnomad SAS
AF:
0.374
Gnomad FIN
AF:
0.469
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.386
Gnomad OTH
AF:
0.307
GnomAD3 exomes
AF:
0.360
AC:
90634
AN:
251442
Hom.:
17425
AF XY:
0.369
AC XY:
50097
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0801
Gnomad AMR exome
AF:
0.362
Gnomad ASJ exome
AF:
0.378
Gnomad EAS exome
AF:
0.319
Gnomad SAS exome
AF:
0.383
Gnomad FIN exome
AF:
0.460
Gnomad NFE exome
AF:
0.380
Gnomad OTH exome
AF:
0.363
GnomAD4 exome
AF:
0.372
AC:
543699
AN:
1460616
Hom.:
103813
Cov.:
39
AF XY:
0.374
AC XY:
271711
AN XY:
726696
show subpopulations
Gnomad4 AFR exome
AF:
0.0734
Gnomad4 AMR exome
AF:
0.355
Gnomad4 ASJ exome
AF:
0.381
Gnomad4 EAS exome
AF:
0.306
Gnomad4 SAS exome
AF:
0.384
Gnomad4 FIN exome
AF:
0.454
Gnomad4 NFE exome
AF:
0.380
Gnomad4 OTH exome
AF:
0.362
GnomAD4 genome
AF:
0.298
AC:
45337
AN:
151916
Hom.:
8212
Cov.:
32
AF XY:
0.306
AC XY:
22729
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.0879
Gnomad4 AMR
AF:
0.309
Gnomad4 ASJ
AF:
0.369
Gnomad4 EAS
AF:
0.318
Gnomad4 SAS
AF:
0.375
Gnomad4 FIN
AF:
0.469
Gnomad4 NFE
AF:
0.386
Gnomad4 OTH
AF:
0.305
Alfa
AF:
0.358
Hom.:
21539
Bravo
AF:
0.281
TwinsUK
AF:
0.370
AC:
1373
ALSPAC
AF:
0.353
AC:
1361
ESP6500AA
AF:
0.0948
AC:
417
ESP6500EA
AF:
0.384
AC:
3304
ExAC
AF:
0.357
AC:
43326
Asia WGS
AF:
0.312
AC:
1083
AN:
3478
EpiCase
AF:
0.375
EpiControl
AF:
0.378

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Fanconi anemia complementation group I Benign:3
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -
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. -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 08, 2016- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Fanconi anemia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.074
.;T;T;T;T;.;T
Eigen
Benign
-0.055
Eigen_PC
Benign
0.097
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.76
T;T;T;T;T;T;T
MetaRNN
Benign
0.0039
T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.2
M;M;.;.;.;M;.
MutationTaster
Benign
4.6e-7
P;P;P;P
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.71
N;N;D;D;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.34
T;T;T;T;T;T;T
Sift4G
Benign
0.078
T;T;T;T;T;T;T
Polyphen
0.75
P;B;.;.;.;.;.
Vest4
0.13
MPC
0.019
ClinPred
0.014
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.075
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.21
Position offset: 31

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: rs17803620; hg19: chr15-89804043; COSMIC: COSV55527083; COSMIC: COSV55527083; API