rs752856233

Variant names:

• chr1-15767441-C-T
• rs752856233
• NM_017556.4:c.316C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-15767441-C-T
• chr1-15767441-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017556.4(FBLIM1):​c.316C>T​(p.Pro106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,392,970 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 0.000027 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26401407).

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.316C>T	p.Pro106Ser	missense	Exon 4 of 9	NP_060026.2	Q8WUP2-1
	FBLIM1	NM_001024215.1		c.316C>T	p.Pro106Ser	missense	Exon 3 of 6	NP_001019386.1	Q8WUP2-2
	FBLIM1	NM_001350151.2		c.316C>T	p.Pro106Ser	missense	Exon 5 of 10	NP_001337080.1	Q8WUP2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLIM1	ENST00000375766.8	TSL:2 MANE Select	c.316C>T	p.Pro106Ser	missense	Exon 4 of 9	ENSP00000364921.3	Q8WUP2-1
	FBLIM1	ENST00000441801.6	TSL:1	c.316C>T	p.Pro106Ser	missense	Exon 3 of 6	ENSP00000416387.2	Q8WUP2-2
	FBLIM1	ENST00000375771.5	TSL:1	c.316C>T	p.Pro106Ser	missense	Exon 5 of 10	ENSP00000364926.1	Q8WUP2-1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 148996 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000673

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: 0.0000447

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 6 AN: 215540 AF XY: 0.0000424

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000656

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000417

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000215 AC: 30 AN: 1392970 Hom.: 0 Cov.: 24 AF XY: 0.0000274 AC XY: 19 AN XY: 694666

African (AFR) AF: 0.00 AC: 0 AN: 30384

American (AMR) AF: 0.0000241 AC: 1 AN: 41460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24784

East Asian (EAS) AF: 0.00 AC: 0 AN: 35562

South Asian (SAS) AF: 0.00 AC: 0 AN: 82778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.0000263 AC: 28 AN: 1062702

Other (OTH) AF: 0.0000173 AC: 1 AN: 57794

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000268 AC: 4 AN: 149114 Hom.: 0 Cov.: 25 AF XY: 0.0000275 AC XY: 2 AN XY: 72684

African (AFR) AF: 0.00 AC: 0 AN: 40444

American (AMR) AF: 0.0000672 AC: 1 AN: 14884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00 AC: 0 AN: 4622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000447 AC: 3 AN: 67162

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.21	T
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0027)
MVP		0.84
MPC		0.79
ClinPred		0.46	T
GERP RS		3.2
Varity_R		0.078
gMVP		0.38
Mutation Taster		=89/11	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: rs752856233; hg19: chr1-16093936;