rs13292454

Positions:

• chr9-95232793-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000136.3(FANCC):​c.345+7856C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,270 control chromosomes in the GnomAD database, including 275 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 0.051 (275 hom., cov: 32)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCC	NM_000136.3	c.345+7856C>T		intron_variant		ENST00000289081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCC	ENST00000289081.8	c.345+7856C>T		intron_variant		1	NM_000136.3	P1

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7740 AN: 152152 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0509 AC: 7748 AN: 152270 Hom.: 275 Cov.: 32 AF XY: 0.0505 AC XY: 3762 AN XY: 74462

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0641 Hom.: 498

Bravo AF: 0.0498

Asia WGS AF: 0.0150 AC: 51 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	3.3
DANN	Benign	0.75

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: rs13292454; hg19: chr9-97995075;