rs1478656876

Variant names:

• chr7-128849968-C-A
• NM_001458.5:c.5200-8C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128849968-C-A
• chr7-128849968-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001458.5(FLNC):​c.5200-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FLNC NM_001458.5 splice_region, intron
• Scores: Splicing: ADA: 0.01457
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5	c.5200-8C>A		splice_region_variant, intron_variant	Intron 30 of 47	ENST00000325888.13	NP_001449.3
FLNC	NM_001127487.2	c.5199+390C>A		intron_variant	Intron 30 of 46		NP_001120959.1
FLNC-AS1	NR_149055.1	n.*194G>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13	c.5200-8C>A		splice_region_variant, intron_variant	Intron 30 of 47	1	NM_001458.5	ENSP00000327145.8
FLNC	ENST00000346177.6	c.5199+390C>A		intron_variant	Intron 30 of 46	1		ENSP00000344002.6
FLNC-AS1	ENST00000469965.1	n.*194G>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430622 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710658

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.015
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128490022;