chr1-15774993-T-G

Variant names:

• chr1-15774993-T-G
• rs902187589
• ENST00000441801.6:c.1087T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024215.1(FBLIM1):​c.1087T>G​(p.Trp363Gly) variant causes a missense 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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W363R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBLIM1 NM_001024215.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06582269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLIM1	NM_017556.4	c.890+197T>G		intron_variant	Intron 7 of 8	ENST00000375766.8	NP_060026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLIM1	ENST00000441801.6	c.1087T>G	p.Trp363Gly	missense_variant	Exon 6 of 6	1		ENSP00000416387.2
FBLIM1	ENST00000375766.8	c.890+197T>G		intron_variant	Intron 7 of 8	2	NM_017556.4	ENSP00000364921.3
FBLIM1	ENST00000375771.5	c.890+197T>G		intron_variant	Intron 8 of 9	1		ENSP00000364926.1
FBLIM1	ENST00000332305.5	c.599+197T>G		intron_variant	Intron 3 of 4	2		ENSP00000364920.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.58
DANN	Benign	0.28
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.018
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.27
MutPred		0.46		Gain of disorder (P = 0.0017);
MVP		0.088
MPC		0.73
ClinPred		0.052	T
GERP RS		-1.7
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs902187589; hg19: chr1-16101488;