16-89793345-T-C

Variant names:

• chr16-89793345-T-C
• rs12921383
• NM_000135.4:c.1007-798A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000135.4(FANCA):​c.1007-798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,268 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (475 hom., cov: 32)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 42 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: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0853 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	NM_000135.4	MANE Select	c.1007-798A>G		intron	N/A	NP_000126.2	O15360-1
	FANCA	NM_001286167.3		c.1007-798A>G		intron	N/A	NP_001273096.1	O15360-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.1007-798A>G		intron	N/A	ENSP00000373952.3	O15360-1
	FANCA	ENST00000567205.2	TSL:1	n.1007-798A>G		intron	N/A	ENSP00000457027.2	H3BT53
	FANCA	ENST00000564475.6	TSL:2	c.1007-798A>G		intron	N/A	ENSP00000454977.2	H3BNS0

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11830 AN: 152148 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0777 AC: 11834 AN: 152268 Hom.: 475 Cov.: 32 AF XY: 0.0770 AC XY: 5734 AN XY: 74464

African (AFR) AF: 0.0657 AC: 2731 AN: 41554

American (AMR) AF: 0.0771 AC: 1179 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.0804 AC: 417 AN: 5188

South Asian (SAS) AF: 0.0586 AC: 283 AN: 4830

European-Finnish (FIN) AF: 0.0787 AC: 835 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5924 AN: 68008

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0325 Hom.: 14

Bravo AF: 0.0801

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.9
DANN	Benign	0.21
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12921383; hg19: chr16-89859753;