dbSNP rs2955795: FAN1:p.His1005His (chr15-30937217-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014967.5(FAN1):c.3015T>C(p.His1005His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,064 control chromosomes in the GnomAD database, including 174,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13700 hom., cov: 32)

Exomes 𝑓: 0.46 ( 160347 hom. )

Consequence

FAN1
NM_014967.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.817

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:

MTMR10 (HGNC:25999): (myotubularin related protein 10) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTMR10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-30937217-T-C is Benign according to our data. Variant chr15-30937217-T-C is described in ClinVar as [Benign]. Clinvar id is 260491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.817 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAN1	NM_014967.5 link	c.3015T>C	p.His1005His	synonymous_variant	Exon 14 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.3015T>C	p.His1005His	synonymous_variant	Exon 14 of 15	1	NM_014967.5	ENSP00000354497.4		Q9Y2M0-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59809

AN:

151922

Hom.:

13685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.515

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.486

AC:

122200

AN:

251342

Hom.:

32262

AF XY:

0.485

AC XY:

65885

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.579

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.851

Gnomad SAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.459

AC:

670839

AN:

1461024

Hom.:

160347

Cov.:

AF XY:

0.460

AC XY:

334310

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.566

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.858

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.471

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.394

AC:

59830

AN:

152040

Hom.:

13700

Cov.:

AF XY:

0.405

AC XY:

30081

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.515

Gnomad4 EAS

AF:

0.851

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.425

Hom.:

10179

Bravo

AF:

0.387

Asia WGS

AF:

0.629

AC:

2187

AN:

3478

EpiCase

AF:

0.440

EpiControl

AF:

0.441

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Karyomegalic interstitial nephritis

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.46

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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