9-95111675-A-G

Position:

chr9-95111675-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000136.3(FANCC):c.1155-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,612,506 control chromosomes in the GnomAD database, including 155,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18407 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137410 hom. )

Consequence

FANCC
NM_000136.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.853

Variant links:

Genes affected

FANCC (HGNC:3584): (FA complementation group C) 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 C. [provided by RefSeq, Jul 2008]

FANCC links:

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

AOPEP links:

FANCC (HGNC:):

FANCC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-95111675-A-G is Benign according to our data. Variant chr9-95111675-A-G is described in ClinVar as [Benign]. Clinvar id is 255273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCC	NM_000136.3 linkuse as main transcript	c.1155-38T>C		intron_variant		ENST00000289081.8	NP_000127.2	Q00597A0A024R9N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000289081.8 linkuse as main transcript	c.1155-38T>C		intron_variant		1	NM_000136.3	ENSP00000289081.3		Q00597

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73636

AN:

152000

Hom.:

18382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.593

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.470

GnomAD3 exomes

AF:

0.473

AC:

118229

AN:

249738

Hom.:

28945

AF XY:

0.464

AC XY:

62781

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.598

Gnomad AMR exome

AF:

0.568

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.624

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.471

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.429

AC:

626693

AN:

1460388

Hom.:

137410

Cov.:

AF XY:

0.429

AC XY:

311445

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.485

AC:

73708

AN:

152118

Hom.:

18407

Cov.:

AF XY:

0.487

AC XY:

36215

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.593

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.445

Hom.:

4177

Bravo

AF:

0.492

Asia WGS

AF:

0.553

AC:

1922

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

DANN

Benign

0.34

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