NM_000135.4:c.1084-29A>G

Variant names:

• chr16-89792097-T-C
• rs6500452
• NM_000135.4:c.1084-29A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000135.4(FANCA):​c.1084-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,442 control chromosomes in the GnomAD database, including 113,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13553 hom., cov: 32)
  • Exomes 𝑓: 0.35 (99939 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.08
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89792097-T-C is Benign according to our data. Variant chr16-89792097-T-C is described in ClinVar as Benign. ClinVar VariationId is 255229.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	NM_000135.4	MANE Select	c.1084-29A>G		intron	N/A	NP_000126.2
	FANCA	NM_001286167.3		c.1084-29A>G		intron	N/A	NP_001273096.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.1084-29A>G		intron	N/A	ENSP00000373952.3
	FANCA	ENST00000567205.2	TSL:1	n.1084-29A>G		intron	N/A	ENSP00000457027.2
	FANCA	ENST00000564475.6	TSL:2	c.1084-29A>G		intron	N/A	ENSP00000454977.2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61237 AN: 151942 Hom.: 13540 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.418 AC: 105168 AN: 251304 AF XY: 0.408

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.749

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.353 AC: 515280 AN: 1461382 Hom.: 99939 Cov.: 39 AF XY: 0.354 AC XY: 257151 AN XY: 727024

African (AFR) AF: 0.513 AC: 17180 AN: 33472

American (AMR) AF: 0.612 AC: 27355 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6345 AN: 26128

East Asian (EAS) AF: 0.816 AC: 32383 AN: 39696

South Asian (SAS) AF: 0.478 AC: 41220 AN: 86246

European-Finnish (FIN) AF: 0.388 AC: 20712 AN: 53382

Middle Eastern (MID) AF: 0.272 AC: 1570 AN: 5764

European-Non Finnish (NFE) AF: 0.312 AC: 347014 AN: 1111628

Other (OTH) AF: 0.356 AC: 21501 AN: 60360

GnomAD4 genome AF: 0.403 AC: 61295 AN: 152060 Hom.: 13553 Cov.: 32 AF XY: 0.415 AC XY: 30867 AN XY: 74324

African (AFR) AF: 0.505 AC: 20957 AN: 41468

American (AMR) AF: 0.479 AC: 7318 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3928 AN: 5176

South Asian (SAS) AF: 0.501 AC: 2416 AN: 4822

European-Finnish (FIN) AF: 0.398 AC: 4201 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20553 AN: 67972

Other (OTH) AF: 0.361 AC: 763 AN: 2114

Alfa AF: 0.334 Hom.: 5576

Bravo AF: 0.417

Asia WGS AF: 0.613 AC: 2133 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group A Benign:2

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 10, 2025

GeneKor MSA

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.096
DANN	Benign	0.35
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6500452; hg19: chr16-89858505; COSMIC: COSV66880734; COSMIC: COSV66880734;