rs357527

Positions:

• chr9-95405529-G-A

Variant summary

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

The XR_930136.3(LOC105376156):​n.329+5927C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 152,206 control chromosomes in the GnomAD database, including 316 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 0.057 (316 hom., cov: 31)
• Consequence: LOC105376156 XR_930136.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

Genes affected

LOC105376156 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376156	XR_930136.3	n.329+5927C>T		intron_variant, non_coding_transcript_variant
LOC105376156	XR_007061677.1	n.329+5927C>T		intron_variant, non_coding_transcript_variant
LOC105376156	XR_007061678.1	n.521+5927C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000636777.1	n.19+21195C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8679 AN: 152088 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0571 AC: 8693 AN: 152206 Hom.: 316 Cov.: 31 AF XY: 0.0574 AC XY: 4271 AN XY: 74426

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0724

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0678 Hom.: 328

Bravo AF: 0.0548

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs357527; hg19: chr9-98167811;