rs114713626

Variant names:

• chr7-128858524-A-G
• rs114713626
• NM_001458.5:c.*1A>G

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.*1A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,610,990 control chromosomes in the GnomAD database, including 1,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (593 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (429 hom.)
• Consequence: FLNC NM_001458.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.997
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-128858524-A-G is Benign according to our data. Variant chr7-128858524-A-G is described in ClinVar as Benign. ClinVar VariationId is 258124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	NM_001458.5	MANE Select	c.*1A>G		3_prime_UTR	Exon 48 of 48	NP_001449.3
	FLNC	NM_001127487.2		c.*1A>G		3_prime_UTR	Exon 47 of 47	NP_001120959.1
	FLNC-AS1	NR_149055.1		n.102+4001T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	ENST00000325888.13	TSL:1 MANE Select	c.*1A>G		3_prime_UTR	Exon 48 of 48	ENSP00000327145.8
	FLNC	ENST00000346177.6	TSL:1	c.*1A>G		3_prime_UTR	Exon 47 of 47	ENSP00000344002.6
	FLNC	ENST00000714185.1		n.*3217A>G		non_coding_transcript_exon	Exon 47 of 47	ENSP00000519474.1

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7211 AN: 151930 Hom.: 592 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0345

GnomAD2 exomes AF: 0.0124 AC: 3091 AN: 248770 AF XY: 0.0101

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00795

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00202

Gnomad OTH exome AF: 0.00612

GnomAD4 exome AF: 0.00603 AC: 8792 AN: 1458942 Hom.: 429 Cov.: 31 AF XY: 0.00556 AC XY: 4037 AN XY: 725934

African (AFR) AF: 0.150 AC: 4902 AN: 32756

American (AMR) AF: 0.00882 AC: 394 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39692

South Asian (SAS) AF: 0.00477 AC: 411 AN: 86148

European-Finnish (FIN) AF: 0.000805 AC: 43 AN: 53410

Middle Eastern (MID) AF: 0.00559 AC: 29 AN: 5184

European-Non Finnish (NFE) AF: 0.00208 AC: 2305 AN: 1110716

Other (OTH) AF: 0.0113 AC: 682 AN: 60242

GnomAD4 genome AF: 0.0475 AC: 7220 AN: 152048 Hom.: 593 Cov.: 32 AF XY: 0.0455 AC XY: 3379 AN XY: 74338

African (AFR) AF: 0.161 AC: 6661 AN: 41406

American (AMR) AF: 0.0209 AC: 320 AN: 15282

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4818

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00210 AC: 143 AN: 67964

Other (OTH) AF: 0.0342 AC: 72 AN: 2108

Alfa AF: 0.0243 Hom.: 111

Bravo AF: 0.0534

EpiCase AF: 0.00185

EpiControl AF: 0.00237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	1	Cardiomyopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs114713626; hg19: chr7-128498578;