chr9-95246099-C-T

Variant names:

• chr9-95246099-C-T
• rs1699499
• NM_000136.3:c.250+1333G>A

Variant summary

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

The NM_000136.3(FANCC):​c.250+1333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 152,320 control chromosomes in the GnomAD database, including 73,802 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 0.98 (73802 hom., cov: 32)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.250+1333G>A		intron	N/A	NP_000127.2
	FANCC	NM_001243743.2		c.250+1333G>A		intron	N/A	NP_001230672.1
	FANCC	NM_001243744.2		c.250+1333G>A		intron	N/A	NP_001230673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.250+1333G>A		intron	N/A	ENSP00000289081.3
	FANCC	ENST00000375305.6	TSL:1	c.250+1333G>A		intron	N/A	ENSP00000364454.1
	FANCC	ENST00000490972.7	TSL:1	c.250+1333G>A		intron	N/A	ENSP00000479931.1

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149814 AN: 152202 Hom.: 73743 Cov.: 32

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.989

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

GnomAD4 genome AF: 0.984 AC: 149932 AN: 152320 Hom.: 73802 Cov.: 32 AF XY: 0.986 AC XY: 73432 AN XY: 74486

African (AFR) AF: 0.996 AC: 41393 AN: 41574

American (AMR) AF: 0.992 AC: 15186 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3440 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.999 AC: 4810 AN: 4816

European-Finnish (FIN) AF: 0.982 AC: 10430 AN: 10624

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66209 AN: 68028

Other (OTH) AF: 0.989 AC: 2093 AN: 2116

Alfa AF: 0.977 Hom.: 50804

Bravo AF: 0.985

Asia WGS AF: 0.999 AC: 3474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.95
DANN	Benign	0.74
PhyloP100		-0.19
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: rs1699499; hg19: chr9-98008381;