rs138158787

Variant names:

• chr1-15777183-G-A
• rs138158787
• NM_017556.4:c.904G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15777183-G-A
• chr1-15777183-G-C
• chr1-15777183-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017556.4(FBLIM1):​c.904G>A​(p.Val302Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,606,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.253
• Publications: 1 publications found

Genes affected

FBLIM1 (HGNC:24686): (filamin binding LIM protein 1) This gene encodes a protein with an N-terminal filamin-binding domain, a central proline-rich domain, and, multiple C-terminal LIM domains. This protein localizes at cell junctions and may link cell adhesion structures to the actin cytoskeleton. This protein may be involved in the assembly and stabilization of actin-filaments and likely plays a role in modulating cell adhesion, cell morphology and cell motility. This protein also localizes to the nucleus and may affect cardiomyocyte differentiation after binding with the CSX/NKX2-5 transcription factor. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SPEN-AS1 (HGNC:55937): (SPEN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04384139).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017556.4. 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
	FBLIM1	NM_017556.4	MANE Select	c.904G>A	p.Val302Ile	missense	Exon 8 of 9	NP_060026.2	Q8WUP2-1
	FBLIM1	NM_001350151.2		c.904G>A	p.Val302Ile	missense	Exon 9 of 10	NP_001337080.1	Q8WUP2-1
	FBLIM1	NM_001024216.3		c.613G>A	p.Val205Ile	missense	Exon 6 of 7	NP_001019387.1	Q8WUP2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLIM1	ENST00000375766.8	TSL:2 MANE Select	c.904G>A	p.Val302Ile	missense	Exon 8 of 9	ENSP00000364921.3	Q8WUP2-1
	FBLIM1	ENST00000375771.5	TSL:1	c.904G>A	p.Val302Ile	missense	Exon 9 of 10	ENSP00000364926.1	Q8WUP2-1
	FBLIM1	ENST00000915887.1		c.976G>A	p.Val326Ile	missense	Exon 9 of 10	ENSP00000585946.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.0000599 AC: 15 AN: 250528 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000454 AC: 66 AN: 1454192 Hom.: 0 Cov.: 30 AF XY: 0.0000360 AC XY: 26 AN XY: 721774

African (AFR) AF: 0.000300 AC: 10 AN: 33372

American (AMR) AF: 0.000158 AC: 7 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85930

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5694

European-Non Finnish (NFE) AF: 0.0000362 AC: 40 AN: 1105804

Other (OTH) AF: 0.0000333 AC: 2 AN: 60024

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152248 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74428

African (AFR) AF: 0.000433 AC: 18 AN: 41554

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.087
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.0
DANN	Benign	0.78
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-0.075	N
PhyloP100		-0.25
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.52		Loss of catalytic residue at V302 (P = 0.1134)
MVP		0.48
ClinPred		0.0077	T
GERP RS		-0.28
Varity_R		0.022
Mutation Taster		=93/7	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: rs138158787; hg19: chr1-16103678; COSMIC: COSV60030143; COSMIC: COSV60030143;