rs2472290

Variant names:

• chr7-128830408-C-A
• rs2472290
• NM_001458.5:c.-230C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128830408-C-A
• chr7-128830408-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001458.5(FLNC):​c.-230C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 151,852 control chromosomes in the GnomAD database, including 75,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75926 hom., cov: 30)
  • Exomes 𝑓: 1.0 (200564 hom.)
  • Failed GnomAD Quality Control
• Consequence: FLNC NM_001458.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11
• Publications: 4 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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, ClinGen, Ambry Genetics
• myofibrillar myopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• myofibrillar myopathy 5

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy 26

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• distal myopathy with posterior leg and anterior hand involvement

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• familial isolated restrictive cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

ENSG00000304163 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-128830408-C-A is Benign according to our data. Variant chr7-128830408-C-A is described in ClinVar as Benign. ClinVar VariationId is 680197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.-230C>A		5_prime_UTR	Exon 1 of 48	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.-230C>A		5_prime_UTR	Exon 1 of 47	NP_001120959.1	Q14315-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	ENST00000325888.13	TSL:1 MANE Select	c.-230C>A		5_prime_UTR	Exon 1 of 48	ENSP00000327145.8	Q14315-1
	FLNC	ENST00000950263.1		c.-230C>A		5_prime_UTR	Exon 1 of 47	ENSP00000620322.1
	FLNC	ENST00000714183.1		c.-230C>A		5_prime_UTR	Exon 1 of 47	ENSP00000519472.1	A0AAQ5BHM3

Frequencies

GnomAD3 genomes AF: 1.00 AC: 151744 AN: 151744 Hom.: 75872 Cov.: 30

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 401136 AN: 401144 Hom.: 200564 Cov.: 3 AF XY: 1.00 AC XY: 211356 AN XY: 211360

African (AFR) AF: 1.00 AC: 7992 AN: 7992

American (AMR) AF: 1.00 AC: 12372 AN: 12374

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 12119 AN: 12120

East Asian (EAS) AF: 1.00 AC: 25888 AN: 25888

South Asian (SAS) AF: 1.00 AC: 38744 AN: 38744

European-Finnish (FIN) AF: 1.00 AC: 29182 AN: 29182

Middle Eastern (MID) AF: 1.00 AC: 1814 AN: 1814

European-Non Finnish (NFE) AF: 1.00 AC: 249291 AN: 249296

Other (OTH) AF: 1.00 AC: 23734 AN: 23734

GnomAD4 genome AF: 1.00 AC: 151852 AN: 151852 Hom.: 75926 Cov.: 30 AF XY: 1.00 AC XY: 74184 AN XY: 74184

African (AFR) AF: 1.00 AC: 41496 AN: 41496

American (AMR) AF: 1.00 AC: 15290 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3462 AN: 3462

East Asian (EAS) AF: 1.00 AC: 5120 AN: 5120

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10540 AN: 10540

Middle Eastern (MID) AF: 1.00 AC: 292 AN: 292

European-Non Finnish (NFE) AF: 1.00 AC: 67802 AN: 67802

Other (OTH) AF: 1.00 AC: 2110 AN: 2110

Alfa AF: 1.00 Hom.: 8165

Bravo AF: 1.00

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
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		1.1
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2472290; hg19: chr7-128470462;