16-89784625-C-T

Position:

• chr16-89784625-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000135.4(FANCA):​c.1470+229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,924 control chromosomes in the GnomAD database, including 2,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2615 hom., cov: 31)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89784625-C-T is Benign according to our data. Variant chr16-89784625-C-T is described in ClinVar as [Benign]. Clinvar id is 1233958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4	c.1470+229G>A		intron_variant		ENST00000389301.8	NP_000126.2
FANCA	NM_001286167.3	c.1470+229G>A		intron_variant			NP_001273096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8	c.1470+229G>A		intron_variant		1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22127 AN: 151806 Hom.: 2611 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.146 AC: 22142 AN: 151924 Hom.: 2615 Cov.: 31 AF XY: 0.159 AC XY: 11805 AN XY: 74226

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.129

Alfa AF: 0.103 Hom.: 3282

Bravo AF: 0.153

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16966142; hg19: chr16-89851033;