rs752828267

Variant names:

• chr1-15765006-G-A
• rs752828267
• NM_017556.4:c.23G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15765006-G-A
• chr1-15765006-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017556.4(FBLIM1):​c.23G>A​(p.Arg8Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,388 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (1 hom.)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.08
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.23G>A	p.Arg8Lys	missense	Exon 3 of 9	NP_060026.2	Q8WUP2-1
	FBLIM1	NM_001024215.1		c.23G>A	p.Arg8Lys	missense	Exon 2 of 6	NP_001019386.1	Q8WUP2-2
	FBLIM1	NM_001350151.2		c.23G>A	p.Arg8Lys	missense	Exon 4 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.23G>A	p.Arg8Lys	missense	Exon 3 of 9	ENSP00000364921.3	Q8WUP2-1
	FBLIM1	ENST00000441801.6	TSL:1	c.23G>A	p.Arg8Lys	missense	Exon 2 of 6	ENSP00000416387.2	Q8WUP2-2
	FBLIM1	ENST00000375771.5	TSL:1	c.23G>A	p.Arg8Lys	missense	Exon 4 of 10	ENSP00000364926.1	Q8WUP2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461388 Hom.: 1 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726966

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111852

Other (OTH) AF: 0.0000331 AC: 2 AN: 60384

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.27
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Benign	2.0	M
PhyloP100		7.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.38		Gain of methylation at R8 (P = 0.0087)
MVP		0.83
MPC		0.78
ClinPred		0.98	D
GERP RS		4.7
PromoterAI		-0.0038	Neutral
Varity_R		0.92
gMVP		0.51
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752828267; hg19: chr1-16091501;