chr1-93529728-C-T

Variant names:

• chr1-93529728-C-T
• rs977875228
• NM_001164473.3:c.482C>T

Variant summary

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

The NM_001164473.3(FNBP1L):​c.482C>T​(p.Thr161Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,526,854 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 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: FNBP1L NM_001164473.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• 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=0.06510264).
• BS2: High AC in GnomAd4 at 9 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.482C>T	p.Thr161Ile	missense	Exon 6 of 17	NP_001157945.1	Q5T0N5-1
	FNBP1L	NM_001024948.3		c.482C>T	p.Thr161Ile	missense	Exon 6 of 14	NP_001020119.1	Q5T0N5-4
	FNBP1L	NM_017737.5		c.482C>T	p.Thr161Ile	missense	Exon 6 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.482C>T	p.Thr161Ile	missense	Exon 6 of 17	ENSP00000271234.7	Q5T0N5-1
	FNBP1L	ENST00000260506.12	TSL:1	c.482C>T	p.Thr161Ile	missense	Exon 6 of 14	ENSP00000260506.8	Q5T0N5-4
	FNBP1L	ENST00000868905.1		c.482C>T	p.Thr161Ile	missense	Exon 6 of 16	ENSP00000538964.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000141 AC: 2 AN: 141928 AF XY: 0.0000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000265

GnomAD4 exome AF: 0.00000582 AC: 8 AN: 1374792 Hom.: 0 Cov.: 28 AF XY: 0.00000295 AC XY: 2 AN XY: 678234

African (AFR) AF: 0.00 AC: 0 AN: 29770

American (AMR) AF: 0.0000699 AC: 2 AN: 28612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24480

East Asian (EAS) AF: 0.00 AC: 0 AN: 35024

South Asian (SAS) AF: 0.00 AC: 0 AN: 72740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071226

Other (OTH) AF: 0.0000698 AC: 4 AN: 57288

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.000524 AC: 8 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000200

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	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Benign	0.14
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	N
PhyloP100		4.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	2.1	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.094
MutPred		0.35		Gain of MoRF binding (P = 0.1274)
MVP		0.20
MPC		0.39
ClinPred		0.16	T
GERP RS		5.7
PromoterAI		-0.011	Neutral
Varity_R		0.082
gMVP		0.093
Mutation Taster		=82/18	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: rs977875228; hg19: chr1-93995285;