rs554879

chr9-95305527-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCC	NM_000136.3	c.-79+11999C>G		intron_variant		ENST00000289081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCC	ENST00000289081.8	c.-79+11999C>G		intron_variant		1	NM_000136.3	P1

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

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.613

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	15
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs554879; hg19: chr9-98067809;