rs13292454

Variant names:

• chr9-95232793-G-A
• rs13292454
• NM_000136.3:c.345+7856C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0797 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.345+7856C>T		intron	N/A	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.345+7856C>T		intron	N/A	NP_001230672.1	A0A024R9N2
	FANCC	NM_001243744.2		c.345+7856C>T		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.345+7856C>T		intron	N/A	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.345+7856C>T		intron	N/A	ENSP00000364454.1	Q00597
	FANCC	ENST00000490972.7	TSL:1	c.345+7856C>T		intron	N/A	ENSP00000479931.1	A0A087WW44

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

African (AFR) AF: 0.0123 AC: 511 AN: 41558

American (AMR) AF: 0.0835 AC: 1278 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4828

European-Finnish (FIN) AF: 0.0783 AC: 830 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4745 AN: 68008

Other (OTH) AF: 0.0426 AC: 90 AN: 2114

Alfa AF: 0.0642 Hom.: 678

Bravo AF: 0.0498

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.75
PhyloP100		-0.24
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: rs13292454; hg19: chr9-97995075;