11-47723005-C-T

Variant names:

• chr11-47723005-C-T
• rs923573810
• NM_015308.5:c.2776G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015308.5(FNBP4):​c.2776G>A​(p.Glu926Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000129 in 1,395,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: FNBP4 NM_015308.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15664881).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP4	NM_015308.5	MANE Select	c.2776G>A	p.Glu926Lys	missense	Exon 15 of 17	NP_056123.2	Q8N3X1-1
	FNBP4	NM_001441100.1		c.3001G>A	p.Glu1001Lys	missense	Exon 16 of 18	NP_001428029.1
	FNBP4	NM_001441101.1		c.3001G>A	p.Glu1001Lys	missense	Exon 16 of 18	NP_001428030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP4	ENST00000263773.10	TSL:1 MANE Select	c.2776G>A	p.Glu926Lys	missense	Exon 15 of 17	ENSP00000263773.5	Q8N3X1-1
	FNBP4	ENST00000917808.1		c.2995G>A	p.Glu999Lys	missense	Exon 16 of 18	ENSP00000587867.1
	FNBP4	ENST00000883715.1		c.2782G>A	p.Glu928Lys	missense	Exon 15 of 17	ENSP00000553774.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000193 AC: 3 AN: 155238 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1395494 Hom.: 0 Cov.: 32 AF XY: 0.00000870 AC XY: 6 AN XY: 689270

African (AFR) AF: 0.0000323 AC: 1 AN: 31006

American (AMR) AF: 0.00 AC: 0 AN: 32716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 36590

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4912

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1079936

Other (OTH) AF: 0.0000173 AC: 1 AN: 57752

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0021	T
Eigen	Benign	0.0066
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.041
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.13	B
Vest4		0.44
MutPred		0.21		Gain of methylation at E926 (P = 4e-04)
MVP		0.25
MPC		0.38
ClinPred		0.27	T
GERP RS		5.3
Varity_R		0.084
gMVP		0.19
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs923573810; hg19: chr11-47744557; COSMIC: COSV55446698; COSMIC: COSV55446698;