16-89816740-A-AGGCCTTGCGTCGT

Position:

• chr16-89816740-A-AGGCCTTGCGTCGT

Variant summary

Our verdict is Benign. Variant got -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. 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 210970.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• 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/exons	MANE	Protein	UniProt
		n.89816740_89816741insGGCCTTGCGTCGT		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000696291.1	n.-138_-126dupACGACGCAAGGCC		non_coding_transcript_exon_variant	1/37			ENSP00000512530.1
FANCA	ENST00000696291.1	n.-138_-126dupACGACGCAAGGCC		5_prime_UTR_variant	1/37			ENSP00000512530.1

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

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.303

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

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.366

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

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 03, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11275235; hg19: chr16-89883148;