rs11227332

Positions:

• chr11-65856268-A-G

Variant summary

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

The ENST00000530413.1(CFL1):​c.-74T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,599,966 control chromosomes in the GnomAD database, including 25,320 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 0.14 (1806 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23514 hom.)
• Consequence: CFL1 ENST00000530413.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFL1	NM_005507.3	c.4-26T>C		intron_variant		ENST00000308162.10	NP_005498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10	c.4-26T>C		intron_variant		1	NM_005507.3	ENSP00000309629.5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21871 AN: 152086 Hom.: 1802 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.149 AC: 36637 AN: 245134 Hom.: 3144 AF XY: 0.149 AC XY: 19824 AN XY: 132622

Gnomad AFR exome AF: 0.0713

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.0576

Gnomad SAS exome AF: 0.0880

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.175 AC: 254044 AN: 1447762 Hom.: 23514 Cov.: 31 AF XY: 0.174 AC XY: 124798 AN XY: 718250

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.0664

Gnomad4 SAS exome AF: 0.0896

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.144 AC: 21885 AN: 152204 Hom.: 1806 Cov.: 31 AF XY: 0.139 AC XY: 10330 AN XY: 74428

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.0822

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.155

Alfa AF: 0.181 Hom.: 3286

Bravo AF: 0.141

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.55
BranchPoint Hunter		6.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11227332; hg19: chr11-65623739;