1-93534786-A-G

Variant names:

• chr1-93534786-A-G
• rs769520098
• NM_001164473.3:c.868A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001164473.3(FNBP1L):​c.868A>G​(p.Ile290Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000637 in 1,570,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12981981).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1L	NM_001164473.3	MANE Select	c.868A>G	p.Ile290Val	missense	Exon 9 of 17	NP_001157945.1	Q5T0N5-1
	FNBP1L	NM_001024948.3		c.868A>G	p.Ile290Val	missense	Exon 9 of 14	NP_001020119.1	Q5T0N5-4
	FNBP1L	NM_017737.5		c.868A>G	p.Ile290Val	missense	Exon 9 of 15	NP_060207.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1L	ENST00000271234.13	TSL:5 MANE Select	c.868A>G	p.Ile290Val	missense	Exon 9 of 17	ENSP00000271234.7	Q5T0N5-1
	FNBP1L	ENST00000260506.12	TSL:1	c.868A>G	p.Ile290Val	missense	Exon 9 of 14	ENSP00000260506.8	Q5T0N5-4
	FNBP1L	ENST00000868905.1		c.868A>G	p.Ile290Val	missense	Exon 9 of 16	ENSP00000538964.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000108 AC: 2 AN: 185430 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000493 AC: 7 AN: 1418738 Hom.: 0 Cov.: 31 AF XY: 0.00000428 AC XY: 3 AN XY: 701430

African (AFR) AF: 0.00 AC: 0 AN: 32542

American (AMR) AF: 0.00 AC: 0 AN: 38594

Ashkenazi Jewish (ASJ) AF: 0.0000785 AC: 2 AN: 25466

East Asian (EAS) AF: 0.00 AC: 0 AN: 37924

South Asian (SAS) AF: 0.00 AC: 0 AN: 80604

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1088232

Other (OTH) AF: 0.00 AC: 0 AN: 58812

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000837 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.10
Sift	Benign	0.69	T
Sift4G	Benign	0.61	T
Polyphen		0.26	B
Vest4		0.27
MutPred		0.39		Loss of catalytic residue at I290 (P = 0.0541)
MVP		0.31
MPC		0.35
ClinPred		0.21	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.36
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs769520098; hg19: chr1-94000343;