rs17788930

Variant names:

• chr11-47731223-A-G
• rs17788930
• NM_015308.5:c.2008+151T>C

Variant summary

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

The NM_015308.5(FNBP4):​c.2008+151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 661,258 control chromosomes in the GnomAD database, including 35,460 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 0.28 (6834 hom., cov: 32)
  • Exomes 𝑓: 0.33 (28626 hom.)
• Consequence: FNBP4 NM_015308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP4	NM_015308.5	c.2008+151T>C		intron_variant	Intron 12 of 16	ENST00000263773.10	NP_056123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP4	ENST00000263773.10	c.2008+151T>C		intron_variant	Intron 12 of 16	1	NM_015308.5	ENSP00000263773.5

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41960 AN: 152032 Hom.: 6822 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.327 AC: 166623 AN: 509108 Hom.: 28626 AF XY: 0.326 AC XY: 84781 AN XY: 260050

Gnomad4 AFR exome AF: 0.0843

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.276 AC: 41986 AN: 152150 Hom.: 6834 Cov.: 32 AF XY: 0.278 AC XY: 20642 AN XY: 74362

Gnomad4 AFR AF: 0.0915

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.300

Alfa AF: 0.319 Hom.: 2464

Bravo AF: 0.271

Asia WGS AF: 0.285 AC: 992 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17788930; hg19: chr11-47752775;