Variant 1-93530747-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001164473.3(FNBP1L):c.511-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,594,810 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 59 hom. )

Consequence

FNBP1L
NM_001164473.3 splice_region, intron

Scores

Splicing: ADA: 0.00003805

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.340

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-93530747-G-T is Benign according to our data. Variant chr1-93530747-G-T is described in ClinVar as [Benign]. Clinvar id is 712674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00716 (10331/1442566) while in subpopulation MID AF= 0.0277 (157/5670). AF 95% confidence interval is 0.0242. There are 59 homozygotes in gnomad4_exome. There are 5250 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 722 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FNBP1L	NM_001164473.3 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant	ENST00000271234.13	NP_001157945.1	Q5T0N5-1B4DSI7
FNBP1L	NM_001024948.3 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant		NP_001020119.1	Q5T0N5-4
FNBP1L	NM_017737.5 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant		NP_060207.2	Q5T0N5-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FNBP1L	ENST00000271234.13 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant	5	NM_001164473.3	ENSP00000271234.7	Q5T0N5-1
FNBP1L	ENST00000260506.12 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant	1		ENSP00000260506.8	Q5T0N5-4
FNBP1L	ENST00000370253.6 linkuse as main transcript	c.511-8G>T	splice_region_variant, intron_variant	5		ENSP00000359275.2	Q5T0N5-3
FNBP1L	ENST00000424449.2 linkuse as main transcript	c.46-8G>T	splice_region_variant, intron_variant	2		ENSP00000397451.2	A0A075B6Q2

Frequencies

GnomAD3 genomes

AF:

0.00475

AC:

722

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00766

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00517

AC:

1160

AN:

224190

Hom.:

AF XY:

0.00582

AC XY:

703

AN XY:

120706

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.00508

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.000145

Gnomad NFE exome

AF:

0.00691

Gnomad OTH exome

AF:

0.00578

GnomAD4 exome

AF:

0.00716

AC:

10331

AN:

1442566

Hom.:

Cov.:

AF XY:

0.00734

AC XY:

5250

AN XY:

715720

show subpopulations

Gnomad4 AFR exome

AF:

0.000664

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00503

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.000437

Gnomad4 NFE exome

AF:

0.00773

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00474

AC:

722

AN:

152244

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00766

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00506

Hom.:

Bravo

AF:

0.00451

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.70

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over