rs12146078

chr1-15770398-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017556.4(FBLIM1):c.542-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,610,146 control chromosomes in the GnomAD database, including 43,212 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 0.18 (2930 hom., cov: 30)
  • Exomes 𝑓: 0.23 (40282 hom.)
• Consequence: FBLIM1 NM_017556.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004923
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLIM1	NM_017556.4	c.542-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLIM1	ENST00000375766.8	c.542-11C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_017556.4	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27891 AN: 151786 Hom.: 2925 Cov.: 30

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.225 AC: 56135 AN: 249430 Hom.: 7347 AF XY: 0.234 AC XY: 31503 AN XY: 134908

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.0671

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.227 AC: 331144 AN: 1458238 Hom.: 40282 Cov.: 32 AF XY: 0.232 AC XY: 168422 AN XY: 725196

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0768

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.184 AC: 27916 AN: 151908 Hom.: 2930 Cov.: 30 AF XY: 0.186 AC XY: 13802 AN XY: 74234

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0767

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.194

Alfa AF: 0.199 Hom.: 652

Bravo AF: 0.184

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.4
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0020
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

Publications

LitVar

Other links and lift over

dbSNP: rs12146078; hg19: chr1-16096893; COSMIC: COSV60029066; COSMIC: COSV60029066;