NM_000136.3:c.-79+19952A>C

Variant names:

• chr9-95297574-T-G
• rs4647376
• NM_000136.3:c.-79+19952A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000136.3(FANCC):​c.-79+19952A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,050 control chromosomes in the GnomAD database, including 39,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (39724 hom., cov: 32)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.512
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-95297574-T-G is Benign according to our data. Variant chr9-95297574-T-G is described in ClinVar as Benign. ClinVar VariationId is 1181066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCC	NM_000136.3	c.-79+19952A>C		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+19952A>C		intron_variant	Intron 1 of 14	1	NM_000136.3	ENSP00000289081.3

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109648 AN: 151932 Hom.: 39705 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.722 AC: 109715 AN: 152050 Hom.: 39724 Cov.: 32 AF XY: 0.721 AC XY: 53546 AN XY: 74302

African (AFR) AF: 0.682 AC: 28285 AN: 41470

American (AMR) AF: 0.735 AC: 11235 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2446 AN: 3464

East Asian (EAS) AF: 0.653 AC: 3370 AN: 5164

South Asian (SAS) AF: 0.684 AC: 3290 AN: 4812

European-Finnish (FIN) AF: 0.767 AC: 8109 AN: 10566

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50555 AN: 67982

Other (OTH) AF: 0.742 AC: 1567 AN: 2112

Alfa AF: 0.733 Hom.: 9668

Bravo AF: 0.715

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.49
PhyloP100		-0.51
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: rs4647376; hg19: chr9-98059856;