16-89777821-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.1826+980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,770 control chromosomes in the GnomAD database, including 13,588 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 0.40 (13588 hom., cov: 30)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.1826+980A>G		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.1826+980A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.1826+980A>G		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61306 AN: 151648 Hom.: 13576 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.404 AC: 61369 AN: 151770 Hom.: 13588 Cov.: 30 AF XY: 0.417 AC XY: 30923 AN XY: 74162

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.363

Alfa AF: 0.320 Hom.: 14206

Bravo AF: 0.418

Asia WGS AF: 0.614 AC: 2135 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	4.3
Dann	Benign	0.74

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: rs1006547; hg19: chr16-89844229;