rs1800286

Variant names:

• chr16-89803353-T-C
• rs1800286
• NM_000135.4:c.710-12A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-89803353-T-C
• chr16-89803353-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.710-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,612,118 control chromosomes in the GnomAD database, including 350,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41010 hom., cov: 32)
  • Exomes 𝑓: 0.64 (309565 hom.)
• Consequence: FANCA NM_000135.4 intron
• Scores: Splicing: ADA: 0.0001637
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.95

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=-0.72).
• BP6: Variant 16-89803353-T-C is Benign according to our data. Variant chr16-89803353-T-C is described in ClinVar as [Benign]. Clinvar id is 255269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89803353-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4	c.710-12A>G		intron_variant	Intron 7 of 42	ENST00000389301.8	NP_000126.2
FANCA	NM_001286167.3	c.710-12A>G		intron_variant	Intron 7 of 42		NP_001273096.1
FANCA	NM_001018112.3	c.710-12A>G		intron_variant	Intron 7 of 10		NP_001018122.1
FANCA	NM_001351830.2	c.614-12A>G		intron_variant	Intron 6 of 9		NP_001338759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8	c.710-12A>G		intron_variant	Intron 7 of 42	1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109012 AN: 151996 Hom.: 40949 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.665

GnomAD3 exomes AF: 0.699 AC: 175544 AN: 251232 Hom.: 63888 AF XY: 0.692 AC XY: 93963 AN XY: 135860

Gnomad AFR exome AF: 0.923

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.989

Gnomad SAS exome AF: 0.796

Gnomad FIN exome AF: 0.680

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.642

GnomAD4 exome AF: 0.644 AC: 940548 AN: 1460004 Hom.: 309565 Cov.: 34 AF XY: 0.647 AC XY: 469764 AN XY: 726362

Gnomad4 AFR exome AF: 0.926

Gnomad4 AMR exome AF: 0.773

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.670

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.717 AC: 109134 AN: 152114 Hom.: 41010 Cov.: 32 AF XY: 0.725 AC XY: 53920 AN XY: 74338

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.669

Alfa AF: 0.628 Hom.: 17374

Bravo AF: 0.729

Asia WGS AF: 0.900 AC: 3131 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group A Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia Benign:2

Nov 18, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jan 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.040
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: rs1800286; hg19: chr16-89869761;