X-14843282-T-C

Variant summary

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

The ENST00000452869.2(FANCB):c.2487+378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,832 control chromosomes in the GnomAD database, including 19,368 homozygotes. There are 20,390 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (15930 hom., 18620 hem., cov: 21)
  • Exomes 𝑓: 0.56 (19368 hom. 20390 hem.)
  • Failed GnomAD Quality Control
• Consequence: FANCB ENST00000452869.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.527

Genes affected

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-14843282-T-C is Benign according to our data. Variant chrX-14843282-T-C is described in ClinVar as [Benign]. Clinvar id is 1282103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001410764.1	c.2487+378A>G		intron_variant
FANCB	XM_017029356.2	c.2487+378A>G		intron_variant
FANCB	XM_047441922.1	c.2487+378A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000452869.2	c.2487+378A>G		intron_variant		1		A2
FANCB	ENST00000696312.1	c.*285A>G		3_prime_UTR_variant	10/10			P2
FANCB	ENST00000696356.1	c.*285A>G		3_prime_UTR_variant	10/10			P2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 67565 AN: 108341 Hom.: 15935 Cov.: 21 AF XY: 0.605 AC XY: 18582 AN XY: 30695

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.559 AC: 84831 AN: 151832 Hom.: 19368 AF XY: 0.544 AC XY: 20390 AN XY: 37452

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.624 AC: 67589 AN: 108384 Hom.: 15930 Cov.: 21 AF XY: 0.606 AC XY: 18620 AN XY: 30748

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.582

Alfa AF: 0.472 Hom.: 2112

Bravo AF: 0.622

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	-0.91
Cadd	Benign	0.94
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2106412; hg19: chrX-14861404;