rs1800345

Positions:

• chr16-89748809-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000135.4(FANCA):​c.3240-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,519,736 control chromosomes in the GnomAD database, including 110,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14368 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95672 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.715

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89748809-C-T is Benign according to our data. Variant chr16-89748809-C-T is described in ClinVar as [Benign]. Clinvar id is 255254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.3240-42G>A		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.3240-42G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.3240-42G>A		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62790 AN: 151836 Hom.: 14350 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.428 AC: 93476 AN: 218474 Hom.: 22633 AF XY: 0.417 AC XY: 49102 AN XY: 117816

Gnomad AFR exome AF: 0.555

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.753

Gnomad SAS exome AF: 0.479

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.357 AC: 488030 AN: 1367782 Hom.: 95672 Cov.: 20 AF XY: 0.358 AC XY: 244329 AN XY: 683166

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.414 AC: 62862 AN: 151954 Hom.: 14368 Cov.: 32 AF XY: 0.425 AC XY: 31581 AN XY: 74242

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.373

Alfa AF: 0.340 Hom.: 1792

Bravo AF: 0.430

Asia WGS AF: 0.615 AC: 2137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 23021409) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Fanconi anemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Fanconi anemia complementation group A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1800345; hg19: chr16-89815217;