16-89748410-T-G

Position:

• chr16-89748410-T-G

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.3348+249A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,148 control chromosomes in the GnomAD database, including 15,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.43 (15340 hom., cov: 33)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.01

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]

FANCA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-89748410-T-G is Benign according to our data. Variant chr16-89748410-T-G is described in ClinVar as [Benign]. Clinvar id is 1279666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4	c.3348+249A>C		intron_variant		ENST00000389301.8	NP_000126.2
FANCA	NM_001286167.3	c.3348+249A>C		intron_variant			NP_001273096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8	c.3348+249A>C		intron_variant		1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64609 AN: 152030 Hom.: 15312 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.425 AC: 64697 AN: 152148 Hom.: 15340 Cov.: 33 AF XY: 0.437 AC XY: 32495 AN XY: 74384

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.379

Alfa AF: 0.306 Hom.: 3436

Bravo AF: 0.445

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.023
DANN	Benign	0.71

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: rs2011877; hg19: chr16-89814818;