rs36204974

chr16-89778770-T-TAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000135.4(FANCA):c.1826+30_1826+31insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,598,144 control chromosomes in the GnomAD database, including 5,628 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (423 hom., cov: 30)
  • Exomes 𝑓: 0.076 (5205 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.384

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 16-89778770-T-TAC is Benign according to our data. Variant chr16-89778770-T-TAC is described in ClinVar as [Benign]. Clinvar id is 255242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.1826+30_1826+31insGT		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.1826+30_1826+31insGT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.1826+30_1826+31insGT		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9086 AN: 151442 Hom.: 422 Cov.: 30

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.0549

GnomAD3 exomes AF: 0.0673 AC: 16922 AN: 251406 Hom.: 1018 AF XY: 0.0664 AC XY: 9029 AN XY: 135884

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.0197

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.0210

Gnomad FIN exome AF: 0.0582

Gnomad NFE exome AF: 0.0768

Gnomad OTH exome AF: 0.0577

GnomAD4 exome AF: 0.0758 AC: 109648 AN: 1446584 Hom.: 5205 Cov.: 29 AF XY: 0.0746 AC XY: 53766 AN XY: 720868

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0562

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.0571

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0803

GnomAD4 genome AF: 0.0600 AC: 9092 AN: 151560 Hom.: 423 Cov.: 30 AF XY: 0.0580 AC XY: 4296 AN XY: 74006

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.0617

Gnomad4 NFE AF: 0.0833

Gnomad4 OTH AF: 0.0552

Alfa AF: 0.0684 Hom.: 76

Bravo AF: 0.0576

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 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: rs36204974; hg19: chr16-89845178;