rs150393409

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014967.5(FAN1):c.1520G>A(p.Arg507His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 1,614,058 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 82 hom. )

Consequence

FAN1
NM_014967.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

FAN1 (HGNC:29170): (FANCD2 and FANCI associated nuclease 1) This gene plays a role in DNA interstrand cross-link repair and encodes a protein with 5' flap endonuclease and 5'-3' exonuclease activity. Mutations in this gene cause karyomegalic interstitial nephritis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2016]

FAN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008552343).

BP6

Variant 15-30910758-G-A is Benign according to our data. Variant chr15-30910758-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 619975.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}. Variant chr15-30910758-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00604 (920/152208) while in subpopulation NFE AF= 0.0099 (673/68004). AF 95% confidence interval is 0.00928. There are 4 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAN1	NM_014967.5 link	c.1520G>A	p.Arg507His	missense_variant	Exon 4 of 15	ENST00000362065.9	NP_055782.3	Q9Y2M0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAN1	ENST00000362065.9 link	c.1520G>A	p.Arg507His	missense_variant	Exon 4 of 15	1	NM_014967.5	ENSP00000354497.4		Q9Y2M0-1

Frequencies

GnomAD3 genomes

AF:

0.00605

AC:

920

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00990

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00656

AC:

1649

AN:

251456

Hom.:

AF XY:

0.00684

AC XY:

930

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.00964

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00920

AC:

13449

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00906

AC XY:

6589

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.0105

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.00348

Gnomad4 FIN exome

AF:

0.00444

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00772

GnomAD4 genome

AF:

0.00604

AC:

920

AN:

152208

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.00990

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00775

Hom.:

Bravo

AF:

0.00624

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00619

AC:

751

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00965

EpiControl

AF:

0.0119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAN1: BP4, BS2 -

Karyomegalic interstitial nephritis

Uncertain:1

Mar 16, 2018

Center for Precision Medicine, Vanderbilt University Medical Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;.;.

Eigen

Benign

-0.050

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

.;D;.;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

M;M;M;M

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

D;N;D;D

REVEL

Benign

0.11

Sift

Benign

0.030

D;D;D;D

Sift4G

Uncertain

0.048

D;T;D;D

Polyphen

0.91

P;P;P;P

Vest4

0.15

MVP

0.43

MPC

0.47

ClinPred

0.019

GERP RS

2.6

Varity_R

0.21

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over