rs75390903

Variant names:

• chr1-15768609-G-A
• rs75390903
• NM_017556.4:c.520G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15768609-G-A
• chr1-15768609-G-C
• chr1-15768609-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017556.4(FBLIM1):​c.520G>A​(p.Val174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,611,988 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (26 hom.)
• Consequence: FBLIM1 NM_017556.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.344
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036016405).
• BP6: Variant 1-15768609-G-A is Benign according to our data. Variant chr1-15768609-G-A is described in ClinVar as Benign. ClinVar VariationId is 782904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00957 (1457/152264) while in subpopulation AFR AF = 0.0332 (1379/41546). AF 95% confidence interval is 0.0317. There are 27 homozygotes in GnomAd4. There are 676 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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.520G>A	p.Val174Ile	missense	Exon 5 of 9	NP_060026.2	Q8WUP2-1
	FBLIM1	NM_001024215.1		c.520G>A	p.Val174Ile	missense	Exon 4 of 6	NP_001019386.1	Q8WUP2-2
	FBLIM1	NM_001350151.2		c.520G>A	p.Val174Ile	missense	Exon 6 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.520G>A	p.Val174Ile	missense	Exon 5 of 9	ENSP00000364921.3	Q8WUP2-1
	FBLIM1	ENST00000441801.6	TSL:1	c.520G>A	p.Val174Ile	missense	Exon 4 of 6	ENSP00000416387.2	Q8WUP2-2
	FBLIM1	ENST00000375771.5	TSL:1	c.520G>A	p.Val174Ile	missense	Exon 6 of 10	ENSP00000364926.1	Q8WUP2-1

Frequencies

GnomAD3 genomes AF: 0.00954 AC: 1452 AN: 152146 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00255 AC: 632 AN: 247480 AF XY: 0.00190

Gnomad AFR exome AF: 0.0338

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.000972 AC: 1419 AN: 1459724 Hom.: 26 Cov.: 31 AF XY: 0.000856 AC XY: 622 AN XY: 726246

African (AFR) AF: 0.0338 AC: 1129 AN: 33390

American (AMR) AF: 0.00213 AC: 94 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.000175 AC: 15 AN: 85914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5758

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111504

Other (OTH) AF: 0.00221 AC: 133 AN: 60282

GnomAD4 genome AF: 0.00957 AC: 1457 AN: 152264 Hom.: 27 Cov.: 32 AF XY: 0.00908 AC XY: 676 AN XY: 74454

African (AFR) AF: 0.0332 AC: 1379 AN: 41546

American (AMR) AF: 0.00314 AC: 48 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68014

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00319 Hom.: 16

Bravo AF: 0.0109

ESP6500AA AF: 0.0320 AC: 141

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00278 AC: 338

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.3
DANN	Benign	0.92
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.34
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.044
Sift	Benign	0.49	T
Sift4G	Benign	0.40	T
Polyphen		0.083	B
Vest4		0.14
MVP		0.49
MPC		0.49
ClinPred		0.0045	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.098
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

Other links and lift over

dbSNP: rs75390903; hg19: chr1-16095104;