rs7039117

Positions:

• chr9-95294898-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000136.3(FANCC):​c.-79+22628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,228,212 control chromosomes in the GnomAD database, including 202 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 0.022 (127 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (75 hom.)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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]

LOC643342 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCC	NM_000136.3	c.-79+22628A>G		intron_variant		ENST00000289081.8	NP_000127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000289081.8	c.-79+22628A>G		intron_variant		1	NM_000136.3	ENSP00000289081.3

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3324 AN: 152192 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00252 AC: 2712 AN: 1075902 Hom.: 75 AF XY: 0.00228 AC XY: 1208 AN XY: 529332

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.00520

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.0000553

Gnomad4 SAS exome AF: 0.000179

Gnomad4 FIN exome AF: 0.0000484

Gnomad4 NFE exome AF: 0.000464

Gnomad4 OTH exome AF: 0.00619

GnomAD4 genome AF: 0.0219 AC: 3336 AN: 152310 Hom.: 127 Cov.: 32 AF XY: 0.0206 AC XY: 1535 AN XY: 74490

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0115 Hom.: 8

Bravo AF: 0.0249

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.80
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs7039117; hg19: chr9-98057180;