rs1800348

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000135.4(FANCA):c.3348+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,551,810 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 30 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 16-89748630-G-A is Benign according to our data. Variant chr16-89748630-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00375 (571/152318) while in subpopulation AMR AF= 0.00641 (98/15296). AF 95% confidence interval is 0.00538. There are 2 homozygotes in gnomad4. There are 258 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4 linkuse as main transcript	c.3348+29C>T		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3 linkuse as main transcript	c.3348+29C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8 linkuse as main transcript	c.3348+29C>T		intron_variant		1	NM_000135.4	P1	O15360-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

572

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00410

AC:

1021

AN:

248722

Hom.:

AF XY:

0.00399

AC XY:

537

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.00442

Gnomad ASJ exome

AF:

0.00779

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00296

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.00709

GnomAD4 exome

AF:

0.00373

AC:

5215

AN:

1399492

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2713

AN XY:

699596

show subpopulations

Gnomad4 AFR exome

AF:

0.00198

Gnomad4 AMR exome

AF:

0.00488

Gnomad4 ASJ exome

AF:

0.00871

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00311

Gnomad4 FIN exome

AF:

0.00484

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00541

GnomAD4 genome

AF:

0.00375

AC:

571

AN:

152318

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

258

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00515

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00591

Hom.:

Bravo

AF:

0.00383

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia complementation group A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

Cadd

Benign

0.86

Dann

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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