rs3780560

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000136.3(FANCC):​c.1534-2386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,286 control chromosomes in the GnomAD database, including 68,196 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 0.95 ( 68196 hom., cov: 34)

Consequence

FANCC
NM_000136.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.331
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FANCCNM_000136.3 linkuse as main transcriptc.1534-2386G>A intron_variant ENST00000289081.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FANCCENST00000289081.8 linkuse as main transcriptc.1534-2386G>A intron_variant 1 NM_000136.3 P1

Frequencies

GnomAD3 genomes
AF:
0.946
AC:
143981
AN:
152168
Hom.:
68139
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.971
Gnomad AMI
AF:
0.973
Gnomad AMR
AF:
0.922
Gnomad ASJ
AF:
0.979
Gnomad EAS
AF:
0.952
Gnomad SAS
AF:
0.940
Gnomad FIN
AF:
0.920
Gnomad MID
AF:
0.991
Gnomad NFE
AF:
0.938
Gnomad OTH
AF:
0.959
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.946
AC:
144098
AN:
152286
Hom.:
68196
Cov.:
34
AF XY:
0.946
AC XY:
70405
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.971
Gnomad4 AMR
AF:
0.922
Gnomad4 ASJ
AF:
0.979
Gnomad4 EAS
AF:
0.951
Gnomad4 SAS
AF:
0.940
Gnomad4 FIN
AF:
0.920
Gnomad4 NFE
AF:
0.938
Gnomad4 OTH
AF:
0.960
Alfa
AF:
0.944
Hom.:
11300
Bravo
AF:
0.947
Asia WGS
AF:
0.946
AC:
3290
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.7
DANN
Benign
0.70

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.

Other links and lift over

dbSNP: rs3780560; hg19: chr9-97866518; API