rs2291567

chr7-128843173-T-Cchr7-128843173-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001458.5(FLNC):c.2551-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,501,336 control chromosomes in the GnomAD database, including 34,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7436 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26920 hom.)
• Consequence: FLNC NM_001458.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.659

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-128843173-T-C is Benign according to our data. Variant chr7-128843173-T-C is described in ClinVar as [Benign]. Clinvar id is 1236146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNC	NM_001458.5	c.2551-56T>C		intron_variant		ENST00000325888.13
FLNC	NM_001127487.2	c.2551-56T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNC	ENST00000325888.13	c.2551-56T>C		intron_variant		1	NM_001458.5	P3
FLNC	ENST00000346177.6	c.2551-56T>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41124 AN: 151938 Hom.: 7414 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.185 AC: 249745 AN: 1349280 Hom.: 26920 Cov.: 24 AF XY: 0.186 AC XY: 124460 AN XY: 668938

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.271 AC: 41182 AN: 152056 Hom.: 7436 Cov.: 33 AF XY: 0.268 AC XY: 19915 AN XY: 74352

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.251

Alfa AF: 0.180 Hom.: 3749

Bravo AF: 0.285

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.43

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: rs2291567; hg19: chr7-128483227; COSMIC: COSV57955032; COSMIC: COSV57955032;