Genetic Variant FNBP4:c.1456+599C>T (chr11-47743354-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_015308.5(FNBP4):c.1456+599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,122 control chromosomes in the GnomAD database, including 37 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 0.020 ( 37 hom., cov: 32)

Consequence

FNBP4
NM_015308.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

1 publications found

Variant links:

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]

FNBP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0196 (2986/152122) while in subpopulation AFR AF = 0.0294 (1221/41508). AF 95% confidence interval is 0.028. There are 37 homozygotes in GnomAd4. There are 1386 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP4	NM_015308.5 link	c.1456+599C>T		intron_variant	Intron 8 of 16	ENST00000263773.10	NP_056123.2	Q8N3X1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNBP4	ENST00000263773.10 link	c.1456+599C>T	intron_variant	Intron 8 of 16	1	NM_015308.5	ENSP00000263773.5	Q8N3X1-1
FNBP4	ENST00000527894.1 link	n.191+599C>T	intron_variant	Intron 1 of 3	3
FNBP4	ENST00000528388.5 link	n.63+599C>T	intron_variant	Intron 1 of 4	2
FNBP4	ENST00000534003.5 link	n.1454+599C>T	intron_variant	Intron 8 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2984

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0225

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

GnomAD4 genome

AF:

0.0196

AC:

2986

AN:

152122

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1386

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0294

AC:

1221

AN:

41508

American (AMR)

AF:

0.0217

AC:

331

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00457

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00613

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0172

AC:

1172

AN:

67992

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

151

302

453

604

755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00559

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.37

(source)

DANN

Benign

0.48

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over