11-47726257-T-C

Variant names:

• chr11-47726257-T-C
• rs11039359
• NM_015308.5:c.2009-1479A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015308.5(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 NM_015308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP4	NM_015308.5	MANE Select	c.2009-1479A>G		intron	N/A	NP_056123.2
	FNBP4	NM_001441100.1		c.2234-1479A>G		intron	N/A	NP_001428029.1
	FNBP4	NM_001441101.1		c.2234-1479A>G		intron	N/A	NP_001428030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP4	ENST00000263773.10	TSL:1 MANE Select	c.2009-1479A>G		intron	N/A	ENSP00000263773.5
	FNBP4	ENST00000530207.1	TSL:2	n.648A>G		non_coding_transcript_exon	Exon 1 of 3
	FNBP4	ENST00000525792.5	TSL:3	n.434-421A>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 2 AN: 40

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0122 AC: 507 AN: 41528

American (AMR) AF: 0.0494 AC: 754 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4818

European-Finnish (FIN) AF: 0.0630 AC: 667 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0679 AC: 4615 AN: 67976

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0625 Hom.: 575

Bravo AF: 0.0445

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.8
DANN	Benign	0.92
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11039359; hg19: chr11-47747809;