16-89793345-T-C

Variant summary

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

The NM_000135.4(FANCA):c.1007-798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,268 control chromosomes in the GnomAD database, including 475 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 0.078 (475 hom., cov: 32)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

Genes affected

FANCA (HGNC:3582): (FA complementation group A) 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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.1007-798A>G		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.1007-798A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.1007-798A>G		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11830 AN: 152148 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0777 AC: 11834 AN: 152268 Hom.: 475 Cov.: 32 AF XY: 0.0770 AC XY: 5734 AN XY: 74464

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0771

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.0804

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0325 Hom.: 14

Bravo AF: 0.0801

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.9
Dann	Benign	0.21

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: rs12921383; hg19: chr16-89859753;