rs665306

Positions:

• chr11-65856554-T-C
• chr11-65856554-T-G

Variant summary

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

The NM_005507.3(CFL1):​c.4-312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 329,726 control chromosomes in the GnomAD database, including 59,190 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 (23763 hom., cov: 32)
  • Exomes 𝑓: 0.62 (35427 hom.)
• Consequence: CFL1 NM_005507.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFL1	NM_005507.3	c.4-312A>G		intron_variant		ENST00000308162.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFL1	ENST00000308162.10	c.4-312A>G		intron_variant		1	NM_005507.3	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80046 AN: 151954 Hom.: 23768 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.618 AC: 109717 AN: 177654 Hom.: 35427 Cov.: 0 AF XY: 0.620 AC XY: 59104 AN XY: 95372

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.526 AC: 80053 AN: 152072 Hom.: 23763 Cov.: 32 AF XY: 0.530 AC XY: 39354 AN XY: 74318

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.560

Alfa AF: 0.581 Hom.: 8785

Bravo AF: 0.493

Asia WGS AF: 0.489 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs665306; hg19: chr11-65624025;