chr16-89816740-A-AGGCCTTGCGTCGTGGCCTTGCGTCGT

Variant names:

• chr16-89816740-A-AGGCCTTGCGTCGTGGCCTTGCGTCGT
• rs11275235
• ENST00000696291.1:n.-126_-125insACGACGCAAGGCCACGACGCAAGGCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000696291.1(FANCA):​n.-126_-125insACGACGCAAGGCCACGACGCAAGGCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 738,658 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: FANCA ENST00000696291.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 7 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696291.1. 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.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		upstream_gene	N/A	NP_000126.2	O15360-1
	FANCA	NM_001286167.3		c.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		upstream_gene	N/A	NP_001273096.1	O15360-3
	FANCA	NM_001018112.3		c.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		upstream_gene	N/A	NP_001018122.1	O15360-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000696291.1		n.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		non_coding_transcript_exon	Exon 1 of 37	ENSP00000512530.1	A0A8Q3WLP8
	FANCA	ENST00000696291.1		n.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		5_prime_UTR	Exon 1 of 37	ENSP00000512530.1	A0A8Q3WLP8
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.-126_-125insACGACGCAAGGCCACGACGCAAGGCC		upstream_gene	N/A	ENSP00000373952.3	O15360-1

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151708 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000426 AC: 25 AN: 586842 Hom.: 0 AF XY: 0.0000429 AC XY: 13 AN XY: 303374

African (AFR) AF: 0.000482 AC: 5 AN: 10380

American (AMR) AF: 0.00 AC: 0 AN: 9552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13042

East Asian (EAS) AF: 0.000213 AC: 5 AN: 23522

South Asian (SAS) AF: 0.0000247 AC: 1 AN: 40506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2196

European-Non Finnish (NFE) AF: 0.0000302 AC: 13 AN: 430370

Other (OTH) AF: 0.0000350 AC: 1 AN: 28536

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151816 Hom.: 0 Cov.: 0 AF XY: 0.000216 AC XY: 16 AN XY: 74188

African (AFR) AF: 0.000627 AC: 26 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000106 Hom.: 257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.028

Splicing

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

Other links and lift over

dbSNP: rs11275235; hg19: chr16-89883148;