rs554879

Variant names:

• chr9-95305527-G-C
• rs554879
• NM_000136.3:c.-79+11999C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000136.3(FANCC):​c.-79+11999C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,046 control chromosomes in the GnomAD database, including 28,121 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 0.61 (28121 hom., cov: 32)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 5 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.-79+11999C>G		intron	N/A	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.-79+11602C>G		intron	N/A	NP_001230672.1	A0A024R9N2
	FANCC	NM_001243744.2		c.-79+11999C>G		intron	N/A	NP_001230673.1	A0A087WW44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.-79+11999C>G		intron	N/A	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.-79+11602C>G		intron	N/A	ENSP00000364454.1	Q00597
	FANCC	ENST00000490972.7	TSL:1	c.-79+11999C>G		intron	N/A	ENSP00000479931.1	A0A087WW44

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92052 AN: 151928 Hom.: 28106 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.606 AC: 92103 AN: 152046 Hom.: 28121 Cov.: 32 AF XY: 0.609 AC XY: 45269 AN XY: 74334

African (AFR) AF: 0.571 AC: 23682 AN: 41440

American (AMR) AF: 0.658 AC: 10059 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2130 AN: 3464

East Asian (EAS) AF: 0.772 AC: 4005 AN: 5190

South Asian (SAS) AF: 0.657 AC: 3172 AN: 4828

European-Finnish (FIN) AF: 0.616 AC: 6494 AN: 10548

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40424 AN: 67966

Other (OTH) AF: 0.613 AC: 1298 AN: 2116

Alfa AF: 0.603 Hom.: 3429

Bravo AF: 0.609

Asia WGS AF: 0.659 AC: 2290 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs554879; hg19: chr9-98067809;