chr1-93534829-A-G

Variant names:

• chr1-93534829-A-G
• rs201882774
• NM_001164473.3:c.911A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001164473.3(FNBP1L):​c.911A>G​(p.Gln304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,578,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.000050 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040242434).
• BS2: High AC in GnomAdExome4 at 71 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.911A>G	p.Gln304Arg	missense	Exon 9 of 17	NP_001157945.1	Q5T0N5-1
	FNBP1L	NM_001024948.3		c.911A>G	p.Gln304Arg	missense	Exon 9 of 14	NP_001020119.1	Q5T0N5-4
	FNBP1L	NM_017737.5		c.911A>G	p.Gln304Arg	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.911A>G	p.Gln304Arg	missense	Exon 9 of 17	ENSP00000271234.7	Q5T0N5-1
	FNBP1L	ENST00000260506.12	TSL:1	c.911A>G	p.Gln304Arg	missense	Exon 9 of 14	ENSP00000260506.8	Q5T0N5-4
	FNBP1L	ENST00000868905.1		c.911A>G	p.Gln304Arg	missense	Exon 9 of 16	ENSP00000538964.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000405 AC: 8 AN: 197582 AF XY: 0.0000571

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000498 AC: 71 AN: 1426314 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 38 AN XY: 705748

African (AFR) AF: 0.00 AC: 0 AN: 32720

American (AMR) AF: 0.000227 AC: 9 AN: 39720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 38206

South Asian (SAS) AF: 0.00 AC: 0 AN: 81000

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000540 AC: 59 AN: 1092834

Other (OTH) AF: 0.0000338 AC: 2 AN: 59162

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000824 Hom.: 2

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000416 AC: 5

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	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.058
Sift	Benign	0.44	T
Sift4G	Benign	0.56	T
Polyphen		0.55	P
Vest4		0.23
MVP		0.37
MPC		0.55
ClinPred		0.099	T
GERP RS		4.2
Varity_R		0.084
gMVP		0.43
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs201882774; hg19: chr1-94000386;