rs3816885

Variant names:

• chr7-128855284-C-T
• rs3816885
• NM_001458.5:c.7221C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-128855284-C-T
• chr7-128855284-C-A
• chr7-128855284-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001458.5(FLNC):​c.7221C>T​(p.Asp2407Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,612,590 control chromosomes in the GnomAD database, including 11,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3624 hom., cov: 33)
  • Exomes 𝑓: 0.068 (7911 hom.)
• Consequence: FLNC NM_001458.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -6.38
• Publications: 19 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-128855284-C-T is Benign according to our data. Variant chr7-128855284-C-T is described in ClinVar as Benign. ClinVar VariationId is 129097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 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.7221C>T	p.Asp2407Asp	synonymous	Exon 43 of 48	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.7122C>T	p.Asp2374Asp	synonymous	Exon 42 of 47	NP_001120959.1	Q14315-2
	FLNC-AS1	NR_149055.1		n.103-1887G>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.7221C>T	p.Asp2407Asp	synonymous	Exon 43 of 48	ENSP00000327145.8	Q14315-1
	FLNC	ENST00000346177.6	TSL:1	c.7122C>T	p.Asp2374Asp	synonymous	Exon 42 of 47	ENSP00000344002.6	Q14315-2
	FLNC	ENST00000950263.1		c.7119C>T	p.Asp2373Asp	synonymous	Exon 42 of 47	ENSP00000620322.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23612 AN: 152032 Hom.: 3617 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.117 AC: 29283 AN: 249516 AF XY: 0.111

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.0182

Gnomad EAS exome AF: 0.361

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0435

Gnomad OTH exome AF: 0.0872

GnomAD4 exome AF: 0.0677 AC: 98835 AN: 1460440 Hom.: 7911 Cov.: 31 AF XY: 0.0692 AC XY: 50255 AN XY: 726642

African (AFR) AF: 0.381 AC: 12737 AN: 33388

American (AMR) AF: 0.154 AC: 6885 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 473 AN: 26132

East Asian (EAS) AF: 0.333 AC: 13230 AN: 39688

South Asian (SAS) AF: 0.167 AC: 14409 AN: 86210

European-Finnish (FIN) AF: 0.0275 AC: 1464 AN: 53186

Middle Eastern (MID) AF: 0.0494 AC: 285 AN: 5764

European-Non Finnish (NFE) AF: 0.0398 AC: 44226 AN: 1111008

Other (OTH) AF: 0.0849 AC: 5126 AN: 60344

GnomAD4 genome AF: 0.155 AC: 23637 AN: 152150 Hom.: 3624 Cov.: 33 AF XY: 0.155 AC XY: 11499 AN XY: 74384

African (AFR) AF: 0.380 AC: 15738 AN: 41448

American (AMR) AF: 0.116 AC: 1771 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1816 AN: 5170

South Asian (SAS) AF: 0.183 AC: 882 AN: 4808

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2873 AN: 68010

Other (OTH) AF: 0.121 AC: 255 AN: 2114

Alfa AF: 0.0813 Hom.: 4695

Bravo AF: 0.172

Asia WGS AF: 0.265 AC: 919 AN: 3478

EpiCase AF: 0.0396

EpiControl AF: 0.0434

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	2	not provided (2)
-	-	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	-0.66
CADD	Benign	0.17
DANN	Benign	0.82
PhyloP100		-6.4
Mutation Taster		=98/2	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: rs3816885; hg19: chr7-128495338; COSMIC: COSV57957812;