rs357527

Variant names:

• chr9-95405529-G-A
• rs357527
• ENST00000636777.1:n.19+21195C>T

Variant summary

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

The ENST00000636777.1(FANCC):​n.19+21195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 152,206 control chromosomes in the GnomAD database, including 316 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 0.057 (316 hom., cov: 31)
• Consequence: FANCC ENST00000636777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• 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

LOC105376156 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376156	NR_188613.1	n.329+5927C>T		intron_variant	Intron 2 of 3
LOC105376156	NR_188614.1	n.329+5927C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000636777.1	n.19+21195C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8679 AN: 152088 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0571 AC: 8693 AN: 152206 Hom.: 316 Cov.: 31 AF XY: 0.0574 AC XY: 4271 AN XY: 74426

African (AFR) AF: 0.0231 AC: 959 AN: 41544

American (AMR) AF: 0.0573 AC: 876 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3464

East Asian (EAS) AF: 0.110 AC: 570 AN: 5170

South Asian (SAS) AF: 0.0335 AC: 161 AN: 4812

European-Finnish (FIN) AF: 0.0884 AC: 937 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4926 AN: 68012

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0657 Hom.: 429

Bravo AF: 0.0548

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.56
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs357527; hg19: chr9-98167811;