14-34711471-AT-A

Position:

• chr14-34711471-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138638.5(CFL2):​c.*1393del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44987 hom., cov: 0)
  • Exomes 𝑓: 0.74 (84848 hom.)
• Consequence: CFL2 NM_138638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527

Genes affected

CFL2 (HGNC:1875): (cofilin 2) This gene encodes an intracellular protein that is involved in the regulation of actin-filament dynamics. This protein is a major component of intranuclear and cytoplasmic actin rods. It can bind G- and F-actin in a 1:1 ratio of cofilin to actin, and it reversibly controls actin polymerization and depolymerization in a pH-dependent manner. Mutations in this gene cause nemaline myopathy type 7, a form of congenital myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-34711471-AT-A is Benign according to our data. Variant chr14-34711471-AT-A is described in ClinVar as [Benign]. Clinvar id is 313083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL2	NM_138638.5	c.*1393del		3_prime_UTR_variant	4/4	ENST00000298159.11	NP_619579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL2	ENST00000298159.11	c.*1393del		3_prime_UTR_variant	4/4	1	NM_138638.5	ENSP00000298159	P1
CFL2	ENST00000341223.8	c.*1393del		3_prime_UTR_variant	4/4	1		ENSP00000340635	P1
CFL2	ENST00000672517.1	c.*1393del		3_prime_UTR_variant	5/5			ENSP00000500532	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115909 AN: 152014 Hom.: 44969 Cov.: 0

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.766

GnomAD3 exomes AF: 0.696 AC: 95075 AN: 136634 Hom.: 35078 AF XY: 0.710 AC XY: 52676 AN XY: 74178

Gnomad AFR exome AF: 0.806

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.828

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.743

Gnomad FIN exome AF: 0.771

Gnomad NFE exome AF: 0.792

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.738 AC: 223077 AN: 302226 Hom.: 84848 Cov.: 0 AF XY: 0.743 AC XY: 128055 AN XY: 172254

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.824

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.741

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.762 AC: 115978 AN: 152128 Hom.: 44987 Cov.: 0 AF XY: 0.757 AC XY: 56297 AN XY: 74388

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.759

Alfa AF: 0.787 Hom.: 8577

Bravo AF: 0.746

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nemaline Myopathy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs5807790; hg19: chr14-35180677;