rs12931267

chr16-89752324-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000135.4(FANCA):c.2982-102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 936,664 control chromosomes in the GnomAD database, including 2,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (210 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2091 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.507

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-89752324-C-G is Benign according to our data. Variant chr16-89752324-C-G is described in ClinVar as [Benign]. Clinvar id is 1267316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCA	NM_000135.4	c.2982-102G>C		intron_variant		ENST00000389301.8
FANCA	NM_001286167.3	c.2982-102G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCA	ENST00000389301.8	c.2982-102G>C		intron_variant		1	NM_000135.4	P1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6954 AN: 152128 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0620 AC: 48670 AN: 784418 Hom.: 2091 AF XY: 0.0596 AC XY: 24822 AN XY: 416610

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0675

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.00496

Gnomad4 FIN exome AF: 0.0559

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.0565

GnomAD4 genome AF: 0.0457 AC: 6953 AN: 152246 Hom.: 210 Cov.: 32 AF XY: 0.0434 AC XY: 3234 AN XY: 74432

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0703 Hom.: 248

Bravo AF: 0.0438

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs12931267; hg19: chr16-89818732;