Genetic Variant FNBP4:c.2008+151T>C (chr11-47731223-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001441113.1(FNBP4):c.*972T>C variant causes a 3 prime UTR 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_001441113.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

31 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=-0.87).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441113.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FNBP4	NM_015308.5	MANE Select	c.2008+151T>C	intron	N/A	NP_056123.2
FNBP4	NM_001441113.1		c.*972T>C	3_prime_UTR	Exon 12 of 12	NP_001428042.1
FNBP4	NM_001441114.1		c.*972T>C	3_prime_UTR	Exon 12 of 12	NP_001428043.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FNBP4	ENST00000263773.10	TSL:1 MANE Select	c.2008+151T>C	intron	N/A	ENSP00000263773.5
FNBP4	ENST00000917808.1		c.2227+151T>C	intron	N/A	ENSP00000587867.1
FNBP4	ENST00000883715.1		c.2014+151T>C	intron	N/A	ENSP00000553774.1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41960

AN:

152032

Hom.:

6822

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0843

AC:

989

AN:

11732

American (AMR)

AF:

0.367

AC:

4270

AN:

11648

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

3529

AN:

12646

East Asian (EAS)

AF:

0.304

AC:

8114

AN:

26724

South Asian (SAS)

AF:

0.262

AC:

7495

AN:

28620

European-Finnish (FIN)

AF:

0.349

AC:

12236

AN:

35110

Middle Eastern (MID)

AF:

0.323

AC:

637

AN:

1974

European-Non Finnish (NFE)

AF:

0.341

AC:

120904

AN:

354126

Other (OTH)

AF:

0.318

AC:

8449

AN:

26528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5347

10694

16041

21388

26735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2260

4520

6780

9040

11300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.276

AC:

41986

AN:

152150

Hom.:

6834

Cov.:

AF XY:

0.278

AC XY:

20642

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0915

AC:

3805

AN:

41564

American (AMR)

AF:

0.364

AC:

5558

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

952

AN:

3466

East Asian (EAS)

AF:

0.305

AC:

1581

AN:

5182

South Asian (SAS)

AF:

0.293

AC:

1414

AN:

4822

European-Finnish (FIN)

AF:

0.341

AC:

3593

AN:

10550

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.349

AC:

23754

AN:

67984

Other (OTH)

AF:

0.300

AC:

631

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1456

2911

4367

5822

7278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.314

Hom.:

4894

Bravo

AF:

0.271

Asia WGS

AF:

0.285

AC:

992

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.16

(source)

DANN

Benign

0.68

PhyloP100

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over