NM_000136.3:c.1534-2386G>A

Variant names:

• chr9-95104236-C-T
• rs3780560
• NM_000136.3:c.1534-2386G>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.1534-2386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,286 control chromosomes in the GnomAD database, including 68,196 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 0.95 (68196 hom., cov: 34)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• 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]

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCC	NM_000136.3	c.1534-2386G>A		intron_variant	Intron 14 of 14	ENST00000289081.8	NP_000127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCC	ENST00000289081.8	c.1534-2386G>A		intron_variant	Intron 14 of 14	1	NM_000136.3	ENSP00000289081.3

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143981 AN: 152168 Hom.: 68139 Cov.: 34

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.946 AC: 144098 AN: 152286 Hom.: 68196 Cov.: 34 AF XY: 0.946 AC XY: 70405 AN XY: 74452

African (AFR) AF: 0.971 AC: 40352 AN: 41566

American (AMR) AF: 0.922 AC: 14098 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 3400 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4915 AN: 5166

South Asian (SAS) AF: 0.940 AC: 4537 AN: 4828

European-Finnish (FIN) AF: 0.920 AC: 9762 AN: 10612

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63829 AN: 68028

Other (OTH) AF: 0.960 AC: 2027 AN: 2112

Alfa AF: 0.944 Hom.: 22464

Bravo AF: 0.947

Asia WGS AF: 0.946 AC: 3290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		0.33
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: rs3780560; hg19: chr9-97866518;