rs6526990

Positions:

• chrX-14826201-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001410764.1(FANCB):​c.2487+17459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 111,444 control chromosomes in the GnomAD database, including 602 homozygotes. There are 2,103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.069 (602 hom., 2103 hem., cov: 23)
• Consequence: FANCB NM_001410764.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCB	NM_001410764.1	c.2487+17459G>A		intron_variant			NP_001397693.1
FANCB	XR_001755672.2	n.2762+17459G>A		intron_variant, non_coding_transcript_variant
FANCB	XR_001755673.2	n.6704+17459G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000696353.1	c.2487+17459G>A		intron_variant				ENSP00000512574	A2
FANCB	ENST00000696354.1	c.2487+17459G>A		intron_variant				ENSP00000512575	A2
FANCB	ENST00000696322.1	c.*1232+17459G>A		intron_variant, NMD_transcript_variant				ENSP00000512559

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 7687 AN: 111393 Hom.: 601 Cov.: 23 AF XY: 0.0620 AC XY: 2084 AN XY: 33613

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.00871

Gnomad EAS AF: 0.00252

Gnomad SAS AF: 0.00992

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0295

Gnomad NFE AF: 0.00662

Gnomad OTH AF: 0.0511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0692 AC: 7711 AN: 111444 Hom.: 602 Cov.: 23 AF XY: 0.0625 AC XY: 2103 AN XY: 33674

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.00871

Gnomad4 EAS AF: 0.00253

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00662

Gnomad4 OTH AF: 0.0557

Alfa AF: 0.0259 Hom.: 419

Bravo AF: 0.0790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6526990; hg19: chrX-14844323;