1-15770439-C-T

Variant names:

• chr1-15770439-C-T
• rs10927851
• NM_017556.4:c.572C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017556.4(FBLIM1):​c.572C>T​(p.Ser191Phe) variant causes a missense change. The variant allele was found at a frequency of 0.701 in 1,612,882 control chromosomes in the GnomAD database, including 400,402 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (30787 hom., cov: 28)
  • Exomes 𝑓: 0.71 (369615 hom.)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73
• Publications: 31 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1763655E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLIM1	NM_017556.4	MANE Select	c.572C>T	p.Ser191Phe	missense	Exon 6 of 9	NP_060026.2
	FBLIM1	NM_001024215.1		c.572C>T	p.Ser191Phe	missense	Exon 5 of 6	NP_001019386.1
	FBLIM1	NM_001350151.2		c.572C>T	p.Ser191Phe	missense	Exon 7 of 10	NP_001337080.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLIM1	ENST00000375766.8	TSL:2 MANE Select	c.572C>T	p.Ser191Phe	missense	Exon 6 of 9	ENSP00000364921.3
	FBLIM1	ENST00000441801.6	TSL:1	c.572C>T	p.Ser191Phe	missense	Exon 5 of 6	ENSP00000416387.2
	FBLIM1	ENST00000375771.5	TSL:1	c.572C>T	p.Ser191Phe	missense	Exon 7 of 10	ENSP00000364926.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94487 AN: 151404 Hom.: 30777 Cov.: 28

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.635

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.688 AC: 172689 AN: 250948 AF XY: 0.691

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.757

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.806

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.683

GnomAD4 exome AF: 0.709 AC: 1035492 AN: 1461362 Hom.: 369615 Cov.: 63 AF XY: 0.709 AC XY: 515291 AN XY: 726960

African (AFR) AF: 0.413 AC: 13805 AN: 33458

American (AMR) AF: 0.749 AC: 33508 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14857 AN: 26132

East Asian (EAS) AF: 0.791 AC: 31417 AN: 39694

South Asian (SAS) AF: 0.724 AC: 62472 AN: 86252

European-Finnish (FIN) AF: 0.628 AC: 33371 AN: 53170

Middle Eastern (MID) AF: 0.626 AC: 3586 AN: 5726

European-Non Finnish (NFE) AF: 0.720 AC: 800725 AN: 1111840

Other (OTH) AF: 0.691 AC: 41751 AN: 60378

GnomAD4 genome AF: 0.624 AC: 94527 AN: 151520 Hom.: 30787 Cov.: 28 AF XY: 0.624 AC XY: 46176 AN XY: 73960

African (AFR) AF: 0.421 AC: 17389 AN: 41320

American (AMR) AF: 0.707 AC: 10762 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4174 AN: 5132

South Asian (SAS) AF: 0.744 AC: 3499 AN: 4706

European-Finnish (FIN) AF: 0.617 AC: 6508 AN: 10544

Middle Eastern (MID) AF: 0.641 AC: 186 AN: 290

European-Non Finnish (NFE) AF: 0.706 AC: 47877 AN: 67838

Other (OTH) AF: 0.638 AC: 1339 AN: 2100

Alfa AF: 0.659 Hom.: 22382

Bravo AF: 0.621

TwinsUK AF: 0.726 AC: 2692

ALSPAC AF: 0.737 AC: 2841

ESP6500AA AF: 0.431 AC: 1898

ESP6500EA AF: 0.712 AC: 6122

ExAC AF: 0.681 AC: 82709

Asia WGS AF: 0.708 AC: 2462 AN: 3478

EpiCase AF: 0.693

EpiControl AF: 0.694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.087
Sift	Benign	0.77	T
Sift4G	Uncertain	0.036	D
Polyphen		0.97	D
Vest4		0.17
MPC		0.87
ClinPred		0.031	T
GERP RS		5.2
Varity_R		0.23
gMVP		0.42
Mutation Taster		=99/1	polymorphism (auto)

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: rs10927851; hg19: chr1-16096934; COSMIC: COSV60030004; COSMIC: COSV60030004;