rs786204633

Variant names:

• chr9-95171080-G-T
• rs781542763
• NM_000136.3:c.520C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-95171080-G-T
• chr9-95171080-G-C
• chr9-95171080-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_000136.3(FANCC):​c.520C>A​(p.Arg174Arg) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000000686 in 1,458,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R174R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FANCC NM_000136.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.004666
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.75
• Publications: 0 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, ClinGen, Labcorp Genetics (formerly Invitae), 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 9-95171080-G-T is Benign according to our data. Variant chr9-95171080-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2463067.Status of the report is criteria_provided_single_submitter, 1 stars.

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.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 15	NP_001230672.1	A0A024R9N2
	FANCC	NM_001243744.2		c.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 14	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.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000490972.7	TSL:1	c.520C>A	p.Arg174Arg	splice_region synonymous	Exon 6 of 14	ENSP00000479931.1	A0A087WW44

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458216 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725702

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108830

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0047
dbscSNV1_RF	Benign	0.11
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: rs781542763; hg19: chr9-97933362;