chr11-65855876-G-A

Position:

• chr11-65855876-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005507.3(CFL1):​c.311+59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,566,118 control chromosomes in the GnomAD database, including 318,422 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (23646 hom., cov: 30)
  • Exomes 𝑓: 0.64 (294776 hom.)
• Consequence: CFL1 NM_005507.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

Genes affected

CFL1 (HGNC:1874): (cofilin 1) The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

CFL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL1	NM_005507.3	c.311+59C>T		intron_variant		ENST00000308162.10	NP_005498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10	c.311+59C>T		intron_variant		1	NM_005507.3	ENSP00000309629.5

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79779 AN: 151700 Hom.: 23651 Cov.: 30

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.638 AC: 901642 AN: 1414300 Hom.: 294776 Cov.: 28 AF XY: 0.640 AC XY: 447128 AN XY: 698324

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.634

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.526 AC: 79786 AN: 151818 Hom.: 23646 Cov.: 30 AF XY: 0.529 AC XY: 39202 AN XY: 74162

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.560

Alfa AF: 0.612 Hom.: 7372

Bravo AF: 0.492

Asia WGS AF: 0.489 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.71

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: rs652021; hg19: chr11-65623347;