Variant 16-89783175-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000135.4(FANCA):c.1471-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,100,878 control chromosomes in the GnomAD database, including 99,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18724 hom., cov: 32)

Exomes 𝑓: 0.39 ( 81126 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.84

Variant links:

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 links:

FANCA (HGNC:):

FANCA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-89783175-C-T is Benign according to our data. Variant chr16-89783175-C-T is described in ClinVar as [Benign]. Clinvar id is 1180470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCA	NM_000135.4 linkuse as main transcript	c.1471-73G>A		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 linkuse as main transcript	c.1471-73G>A		intron_variant			NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.1471-73G>A		intron_variant		1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70368

AN:

151900

Hom.:

18703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.391

AC:

370716

AN:

948860

Hom.:

81126

AF XY:

0.393

AC XY:

193240

AN XY:

491426

show subpopulations

Gnomad4 AFR exome

AF:

0.694

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.829

Gnomad4 SAS exome

AF:

0.565

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.463

AC:

70449

AN:

152018

Hom.:

18724

Cov.:

AF XY:

0.475

AC XY:

35281

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.761

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.312

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.367

Hom.:

2759

Bravo

AF:

0.481

Asia WGS

AF:

0.672

AC:

2336

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

-0.93

CADD

Benign

0.31

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over