9-95424044-C-T

Variant names:

• chr9-95424044-C-T
• rs357552
• ENST00000433644.2:n.73+2680G>A

Variant summary

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

The ENST00000433644.2(FANCC):​n.73+2680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,118 control chromosomes in the GnomAD database, including 35,059 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 0.67 (35059 hom., cov: 33)
• Consequence: FANCC ENST00000433644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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]

LOC105376156 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376156	NR_188613.1	n.107+2680G>A		intron_variant	Intron 1 of 3
LOC105376156	NR_188614.1	n.107+2680G>A		intron_variant	Intron 1 of 2
LOC105376156	NR_188615.1	n.108-752G>A		intron_variant	Intron 1 of 2
LOC105376156	NR_188616.1	n.107+2680G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000433644.2	n.73+2680G>A		intron_variant	Intron 1 of 1	2
FANCC	ENST00000636777.1	n.19+2680G>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102438 AN: 152000 Hom.: 35043 Cov.: 33

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.674 AC: 102511 AN: 152118 Hom.: 35059 Cov.: 33 AF XY: 0.666 AC XY: 49492 AN XY: 74362

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.664

Alfa AF: 0.635 Hom.: 5752

Bravo AF: 0.671

Asia WGS AF: 0.510 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs357552; hg19: chr9-98186326;