rs11275235

Variant names:

• chr16-89816740-A-AGGCCTTGCGTCGT
• rs11275235
• ENST00000696291.1:n.-138_-126dupACGACGCAAGGCC

Your query was ambiguous. Multiple possible variants found:

• chr16-89816740-A-AGGCCTTGCGTCGT
• chr16-89816740-A-AGGCCTTGCGTCGTGGCCTTGCGTCGT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000696291.1(FANCA):​n.-138_-126dupACGACGCAAGGCC 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 0.299 in 738,330 control chromosomes in the GnomAD database, including 48,270 homozygotes. 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. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (13446 hom., cov: 0)
  • Exomes 𝑓: 0.27 (34824 hom.)
• Consequence: FANCA ENST00000696291.1 non_coding_transcript_exon
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• 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: 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 -9 ACMG points.

• BP6: Variant 16-89816740-A-AGGCCTTGCGTCGT is Benign according to our data. Variant chr16-89816740-A-AGGCCTTGCGTCGT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210970.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4	c.-126_-125insACGACGCAAGGCC		upstream_gene_variant		ENST00000389301.8	NP_000126.2
FANCA	NM_001286167.3	c.-126_-125insACGACGCAAGGCC		upstream_gene_variant			NP_001273096.1
FANCA	NM_001018112.3	c.-126_-125insACGACGCAAGGCC		upstream_gene_variant			NP_001018122.1
FANCA	NM_001351830.2	c.-126_-125insACGACGCAAGGCC		upstream_gene_variant			NP_001338759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8	c.-138_-126dupACGACGCAAGGCC		upstream_gene_variant		1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60008 AN: 151656 Hom.: 13435 Cov.: 0

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.274 AC: 160662 AN: 586566 Hom.: 34824 AF XY: 0.281 AC XY: 85164 AN XY: 303226

African (AFR) AF: 0.410 AC: 4258 AN: 10376

American (AMR) AF: 0.462 AC: 4416 AN: 9550

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 2302 AN: 13038

East Asian (EAS) AF: 0.958 AC: 22517 AN: 23514

South Asian (SAS) AF: 0.407 AC: 16497 AN: 40498

European-Finnish (FIN) AF: 0.360 AC: 10350 AN: 28726

Middle Eastern (MID) AF: 0.206 AC: 451 AN: 2192

European-Non Finnish (NFE) AF: 0.212 AC: 91227 AN: 430144

Other (OTH) AF: 0.303 AC: 8644 AN: 28528

GnomAD4 genome AF: 0.396 AC: 60058 AN: 151764 Hom.: 13446 Cov.: 0 AF XY: 0.407 AC XY: 30193 AN XY: 74162

African (AFR) AF: 0.473 AC: 19596 AN: 41422

American (AMR) AF: 0.465 AC: 7101 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3470

East Asian (EAS) AF: 0.969 AC: 4941 AN: 5100

South Asian (SAS) AF: 0.475 AC: 2282 AN: 4808

European-Finnish (FIN) AF: 0.379 AC: 3996 AN: 10540

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20416 AN: 67854

Other (OTH) AF: 0.366 AC: 769 AN: 2102

Alfa AF: 0.162 Hom.: 257

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

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;