rs652021

Positions:

• chr11-65855876-G-A
• chr11-65855876-G-C

Variant summary

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

The ENST00000308162.10(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 ENST00000308162.10 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]

SNX32 (HGNC:26423): (sorting nexin 32) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

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	P1

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;