ENST00000433644.2:n.73+2680G>A

Variant names:

• chr9-95424044-C-T
• rs357552
• ENST00000433644.2:n.73+2680G>A

Variant summary

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

The ENST00000433644.2(FANCC):​n.73+2680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,118 control chromosomes in the GnomAD database, including 35,059 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 0.67 (35059 hom., cov: 33)
• Consequence: FANCC ENST00000433644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 1 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

LOC105376156 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433644.2. 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
	LOC105376156	NR_188613.1		n.107+2680G>A		intron	N/A
	LOC105376156	NR_188614.1		n.107+2680G>A		intron	N/A
	LOC105376156	NR_188615.1		n.108-752G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000433644.2	TSL:2	n.73+2680G>A		intron	N/A
	FANCC	ENST00000636777.1	TSL:5	n.19+2680G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102438 AN: 152000 Hom.: 35043 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.674 AC: 102511 AN: 152118 Hom.: 35059 Cov.: 33 AF XY: 0.666 AC XY: 49492 AN XY: 74362

African (AFR) AF: 0.724 AC: 30038 AN: 41492

American (AMR) AF: 0.555 AC: 8477 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2332 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2458 AN: 5182

South Asian (SAS) AF: 0.472 AC: 2277 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6880 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47796 AN: 67992

Other (OTH) AF: 0.664 AC: 1400 AN: 2108

Alfa AF: 0.655 Hom.: 10710

Bravo AF: 0.671

Asia WGS AF: 0.510 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.36
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs357552; hg19: chr9-98186326;