chr9-95111675-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FANCC	NM_000136.3 link	c.1155-38T>C		intron_variant	Intron 12 of 14	ENST00000289081.8	NP_000127.2	Q00597A0A024R9N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000289081.8 link	c.1155-38T>C		intron_variant	Intron 12 of 14	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

GnomAD2 exomes

AF:

0.473

AC:

118229

AN:

249738

AF XY:

0.464

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 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

African (AFR)

AF:

0.596

AC:

19931

AN:

33444

American (AMR)

AF:

0.562

AC:

25098

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8717

AN:

26124

East Asian (EAS)

AF:

0.611

AC:

24262

AN:

39696

South Asian (SAS)

AF:

0.466

AC:

40221

AN:

86226

European-Finnish (FIN)

AF:

0.474

AC:

25223

AN:

53186

Middle Eastern (MID)

AF:

0.409

AC:

2356

AN:

5764

European-Non Finnish (NFE)

AF:

0.410

AC:

455043

AN:

1110904

Other (OTH)

AF:

0.428

AC:

25842

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

20017

40035

60052

80070

100087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14212

28424

42636

56848

71060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.485

AC:

73708

AN:

152118

Hom.:

18407

Cov.:

AF XY:

0.487

AC XY:

36215

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.593

AC:

24590

AN:

41492

American (AMR)

AF:

0.511

AC:

7817

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1157

AN:

3468

East Asian (EAS)

AF:

0.626

AC:

3235

AN:

5170

South Asian (SAS)

AF:

0.498

AC:

2401

AN:

4824

European-Finnish (FIN)

AF:

0.465

AC:

4914

AN:

10578

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.412

AC:

28033

AN:

67966

Other (OTH)

AF:

0.476

AC:

1007

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1938

3876

5814

7752

9690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group C

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Apr 10, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

(source)

DANN

Benign

0.34

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over