9-95302247-T-C

Variant names:

• chr9-95302247-T-C
• rs356664
• NM_000136.3:c.-79+15279A>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+15279A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,996 control chromosomes in the GnomAD database, including 33,648 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 0.66 (33648 hom., cov: 32)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 2 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
• 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 (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCC	NM_000136.3	c.-79+15279A>G		intron_variant	Intron 1 of 14	ENST00000289081.8	NP_000127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000289081.8	c.-79+15279A>G		intron_variant	Intron 1 of 14	1	NM_000136.3	ENSP00000289081.3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100343 AN: 151878 Hom.: 33611 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.661 AC: 100432 AN: 151996 Hom.: 33648 Cov.: 32 AF XY: 0.663 AC XY: 49254 AN XY: 74276

African (AFR) AF: 0.751 AC: 31125 AN: 41438

American (AMR) AF: 0.678 AC: 10347 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3470

East Asian (EAS) AF: 0.816 AC: 4227 AN: 5178

South Asian (SAS) AF: 0.701 AC: 3379 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6490 AN: 10536

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

European-Non Finnish (NFE) AF: 0.596 AC: 40505 AN: 67966

Other (OTH) AF: 0.655 AC: 1385 AN: 2114

Alfa AF: 0.573 Hom.: 3771

Bravo AF: 0.669

Asia WGS AF: 0.725 AC: 2524 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	7.6
DANN	Benign	0.47
PhyloP100		-0.59
Mutation Taster		=99/1	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: rs356664; hg19: chr9-98064529;