1-15774908-G-T

Variant names:

• chr1-15774908-G-T
• rs12093675
• ENST00000441801.6:c.1002G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001024215.1(FBLIM1):​c.1002G>T​(p.Leu334Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L334L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBLIM1 NM_001024215.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=0.776 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024215.1. 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.890+112G>T		intron	N/A	NP_060026.2	Q8WUP2-1
	FBLIM1	NM_001024215.1		c.1002G>T	p.Leu334Leu	synonymous	Exon 6 of 6	NP_001019386.1	Q8WUP2-2
	FBLIM1	NM_001350151.2		c.890+112G>T		intron	N/A	NP_001337080.1	Q8WUP2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLIM1	ENST00000441801.6	TSL:1	c.1002G>T	p.Leu334Leu	synonymous	Exon 6 of 6	ENSP00000416387.2	Q8WUP2-2
	FBLIM1	ENST00000375766.8	TSL:2 MANE Select	c.890+112G>T		intron	N/A	ENSP00000364921.3	Q8WUP2-1
	FBLIM1	ENST00000375771.5	TSL:1	c.890+112G>T		intron	N/A	ENSP00000364926.1	Q8WUP2-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12093675; hg19: chr1-16101403;