rs11039359

Positions:

• chr11-47726257-T-C

Variant summary

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

The ENST00000263773.10(FNBP4):​c.2009-1479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,198 control chromosomes in the GnomAD database, including 245 homozygotes. 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 0.046 (245 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: FNBP4 ENST00000263773.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

Genes affected

FNBP4 (HGNC:19752): (formin binding protein 4) This gene encodes a protein containing two tryptophan-rich WW domains that binds the proline-rich formin homology 1 domains of formin family proteins, suggesting a role in the regulation of cytoskeletal dynamics during cell division and migration. It also binds intersectin family proteins suggesting a role in the maintenance of membrane curvature at sites of nascent vesicle formation. Naturally occurring mutations in this gene are associated with Waardenburg anophthalmia syndrome. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP4	NM_015308.5	c.2009-1479A>G		intron_variant		ENST00000263773.10	NP_056123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNBP4	ENST00000263773.10	c.2009-1479A>G		intron_variant		1	NM_015308.5	ENSP00000263773	P1
FNBP4	ENST00000530207.1	n.648A>G		non_coding_transcript_exon_variant	1/3	2
FNBP4	ENST00000525792.5	n.434-421A>G		intron_variant, non_coding_transcript_variant		3
FNBP4	ENST00000531394.1	n.331-1479A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6981 AN: 152032 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0417 AC: 2 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0500

GnomAD4 genome AF: 0.0459 AC: 6978 AN: 152150 Hom.: 245 Cov.: 32 AF XY: 0.0445 AC XY: 3311 AN XY: 74384

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0643 Hom.: 467

Bravo AF: 0.0445

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.8
DANN	Benign	0.92

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: rs11039359; hg19: chr11-47747809;