NM_001164473.3:c.511-8G>T

Variant names:

• chr1-93530747-G-T
• rs199743116
• NM_001164473.3:c.511-8G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 16	ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 13		NP_001020119.1
FNBP1L	NM_017737.5	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 14		NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 16	5	NM_001164473.3	ENSP00000271234.7
FNBP1L	ENST00000260506.12	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 13	1		ENSP00000260506.8
FNBP1L	ENST00000370253.6	c.511-8G>T		splice_region_variant, intron_variant	Intron 6 of 14	5		ENSP00000359275.2
FNBP1L	ENST00000424449.2	c.46-8G>T		splice_region_variant, intron_variant	Intron 1 of 11	2		ENSP00000397451.2

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 722 AN: 152126 Hom.: 3 Cov.: 32

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.: 8 AF XY: 0.00582 AC XY: 703 AN XY: 120706

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.: 59 Cov.: 30 AF XY: 0.00734 AC XY: 5250 AN XY: 715720

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.: 3 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74452

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.: 2

Bravo AF: 0.00451

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs199743116; hg19: chr1-93996304;