14-34711471-AT-A

Variant names:

• chr14-34711471-AT-A
• rs5807790
• NM_138638.5:c.*1393delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138638.5(CFL2):​c.*1393delA 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
• Publications: 2 publications found

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]

CFL2 Gene-Disease associations (from GenCC):

• nemaline myopathy 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• typical nemaline myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138638.5. 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
	CFL2	NM_138638.5	MANE Select	c.*1393delA		3_prime_UTR	Exon 4 of 4	NP_619579.1	Q549N0
	CFL2	NM_021914.8		c.*1393delA		3_prime_UTR	Exon 4 of 4	NP_068733.1	Q9Y281-1
	CFL2	NM_001243645.2		c.*1393delA		3_prime_UTR	Exon 4 of 4	NP_001230574.1	Q9Y281-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFL2	ENST00000298159.11	TSL:1 MANE Select	c.*1393delA		3_prime_UTR	Exon 4 of 4	ENSP00000298159.6	Q9Y281-1
	CFL2	ENST00000341223.8	TSL:1	c.*1393delA		3_prime_UTR	Exon 4 of 4	ENSP00000340635.3	Q9Y281-1
	CFL2	ENST00000672517.1		c.*1393delA		3_prime_UTR	Exon 5 of 5	ENSP00000500532.1	Q9Y281-1

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

GnomAD2 exomes AF: 0.696 AC: 95075 AN: 136634 AF XY: 0.710

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 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

African (AFR) AF: 0.807 AC: 6907 AN: 8554

American (AMR) AF: 0.492 AC: 13415 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 8883 AN: 10786

East Asian (EAS) AF: 0.340 AC: 3128 AN: 9210

South Asian (SAS) AF: 0.741 AC: 44217 AN: 59648

European-Finnish (FIN) AF: 0.771 AC: 9860 AN: 12790

Middle Eastern (MID) AF: 0.834 AC: 959 AN: 1150

European-Non Finnish (NFE) AF: 0.788 AC: 125124 AN: 158768

Other (OTH) AF: 0.754 AC: 10584 AN: 14046

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

African (AFR) AF: 0.803 AC: 33343 AN: 41514

American (AMR) AF: 0.651 AC: 9950 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2854 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1766 AN: 5166

South Asian (SAS) AF: 0.720 AC: 3475 AN: 4826

European-Finnish (FIN) AF: 0.773 AC: 8173 AN: 10568

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53919 AN: 67990

Other (OTH) AF: 0.759 AC: 1602 AN: 2112

Alfa AF: 0.787 Hom.: 8577

Bravo AF: 0.746

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Nemaline Myopathy, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5807790; hg19: chr14-35180677; COSMIC: COSV53310709; COSMIC: COSV53310709;