rs117517372

Variant names:

• chr7-128851284-C-T
• rs117517372
• NM_001458.5:c.5592C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001458.5(FLNC):​c.5592C>T​(p.Ala1864Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,614,134 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (167 hom.)
• Consequence: FLNC NM_001458.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.319
• Publications: 2 publications found

Genes affected

FLNC (HGNC:3756): (filamin C) This gene encodes one of three related filamin genes, specifically gamma filamin. These filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. Three functional domains exist in filamin: an N-terminal filamentous actin-binding domain, a C-terminal self-association domain, and a membrane glycoprotein-binding domain. Mutations in this gene are a cause of cardiopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2022]

FLNC-AS1 (HGNC:53474): (FLNC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-128851284-C-T is Benign according to our data. Variant chr7-128851284-C-T is described in ClinVar as Benign. ClinVar VariationId is 129093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.319 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001458.5. 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
	FLNC	NM_001458.5	MANE Select	c.5592C>T	p.Ala1864Ala	synonymous	Exon 34 of 48	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.5493C>T	p.Ala1831Ala	synonymous	Exon 33 of 47	NP_001120959.1	Q14315-2
	FLNC-AS1	NR_149055.1		n.315+117G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	ENST00000325888.13	TSL:1 MANE Select	c.5592C>T	p.Ala1864Ala	synonymous	Exon 34 of 48	ENSP00000327145.8	Q14315-1
	FLNC	ENST00000346177.6	TSL:1	c.5493C>T	p.Ala1831Ala	synonymous	Exon 33 of 47	ENSP00000344002.6	Q14315-2
	FLNC	ENST00000950263.1		c.5490C>T	p.Ala1830Ala	synonymous	Exon 33 of 47	ENSP00000620322.1

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 398 AN: 152216 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00755 AC: 1884 AN: 249488 AF XY: 0.00932

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00368 AC: 5375 AN: 1461800 Hom.: 167 Cov.: 33 AF XY: 0.00500 AC XY: 3633 AN XY: 727204

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0189 AC: 752 AN: 39700

South Asian (SAS) AF: 0.0498 AC: 4299 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111998

Other (OTH) AF: 0.00462 AC: 279 AN: 60394

GnomAD4 genome AF: 0.00259 AC: 394 AN: 152334 Hom.: 12 Cov.: 33 AF XY: 0.00383 AC XY: 285 AN XY: 74488

African (AFR) AF: 0.000192 AC: 8 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0206 AC: 107 AN: 5182

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.000854

Asia WGS AF: 0.0400 AC: 138 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		-0.32
Mutation Taster		=73/27	polymorphism (auto)

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: rs117517372; hg19: chr7-128491338;