Genetic Variant FANCC:n.73+2680G>A (chr9-95424044-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000433644.2(FANCC):n.73+2680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,118 control chromosomes in the GnomAD database, including 35,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35059 hom., cov: 33)

Consequence

FANCC
ENST00000433644.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

1 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 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group C
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
colorectal cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
malignant pancreatic neoplasm
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
ovarian cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
prostate cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

FANCC links:

LOC105376156 (HGNC:):

LOC105376156 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433644.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
LOC105376156	NR_188613.1	n.107+2680G>A	intron	N/A
LOC105376156	NR_188614.1	n.107+2680G>A	intron	N/A
LOC105376156	NR_188615.1	n.108-752G>A	intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000433644.2	TSL:2	n.73+2680G>A		intron	N/A
	FANCC	ENST00000636777.1	TSL:5	n.19+2680G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102438

AN:

152000

Hom.:

35043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.724

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.651

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.674

AC:

102511

AN:

152118

Hom.:

35059

Cov.:

AF XY:

0.666

AC XY:

49492

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.724

AC:

30038

AN:

41492

American (AMR)

AF:

0.555

AC:

8477

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2332

AN:

3466

East Asian (EAS)

AF:

0.474

AC:

2458

AN:

5182

South Asian (SAS)

AF:

0.472

AC:

2277

AN:

4820

European-Finnish (FIN)

AF:

0.651

AC:

6880

AN:

10570

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.703

AC:

47796

AN:

67992

Other (OTH)

AF:

0.664

AC:

1400

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1692

3385

5077

6770

8462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.655

Hom.:

10710

Bravo

AF:

0.671

Asia WGS

AF:

0.510

AC:

1779

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.25

(source)

DANN

Benign

0.36

PhyloP100

-1.4

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over