Genetic Variant FNBP1L:c.1275-112G>A (chr1-93546730-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001164473.3(FNBP1L):c.1275-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,098,556 control chromosomes in the GnomAD database, including 380,533 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 0.83 ( 52902 hom., cov: 31)

Exomes 𝑓: 0.83 ( 327631 hom. )

Consequence

FNBP1L
NM_001164473.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Publications

3 publications found

Variant links:

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FNBP1L 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FNBP1L	NM_001164473.3	MANE Select	c.1275-112G>A	intron	N/A	NP_001157945.1
FNBP1L	NM_001024948.3		c.1101-112G>A	intron	N/A	NP_001020119.1
FNBP1L	NM_017737.5		c.1101-112G>A	intron	N/A	NP_060207.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FNBP1L	ENST00000271234.13	TSL:5 MANE Select	c.1275-112G>A	intron	N/A	ENSP00000271234.7
FNBP1L	ENST00000260506.12	TSL:1	c.1101-112G>A	intron	N/A	ENSP00000260506.8
FNBP1L	ENST00000868905.1		c.1260-112G>A	intron	N/A	ENSP00000538964.1

Frequencies

GnomAD3 genomes

AF:

0.832

AC:

126463

AN:

151968

Hom.:

52847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.852

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.973

Gnomad FIN

AF:

0.855

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.839

GnomAD4 exome

AF:

0.830

AC:

785297

AN:

946470

Hom.:

327631

AF XY:

0.834

AC XY:

401550

AN XY:

481286

show subpopulations

African (AFR)

AF:

0.826

AC:

17148

AN:

20758

American (AMR)

AF:

0.887

AC:

19725

AN:

22246

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

15096

AN:

19192

East Asian (EAS)

AF:

1.00

AC:

33850

AN:

33856

South Asian (SAS)

AF:

0.971

AC:

58305

AN:

60048

European-Finnish (FIN)

AF:

0.843

AC:

39061

AN:

46310

Middle Eastern (MID)

AF:

0.840

AC:

3035

AN:

3612

European-Non Finnish (NFE)

AF:

0.808

AC:

563979

AN:

698088

Other (OTH)

AF:

0.829

AC:

35098

AN:

42360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6402

12805

19207

25610

32012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11046

22092

33138

44184

55230

<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:

0.832

AC:

126578

AN:

152086

Hom.:

52902

Cov.:

AF XY:

0.836

AC XY:

62142

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.824

AC:

34166

AN:

41474

American (AMR)

AF:

0.852

AC:

13013

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

2744

AN:

3466

East Asian (EAS)

AF:

0.999

AC:

5187

AN:

5192

South Asian (SAS)

AF:

0.972

AC:

4697

AN:

4830

European-Finnish (FIN)

AF:

0.855

AC:

9048

AN:

10580

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.810

AC:

55031

AN:

67956

Other (OTH)

AF:

0.840

AC:

1775

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1078

2155

3233

4310

5388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<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:

0.815

Hom.:

99018

Bravo

AF:

0.829

Asia WGS

AF:

0.970

AC:

3375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.37

(source)

DANN

Benign

0.69

PhyloP100

-0.23

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