ENST00000530413.1:c.-74T>C

Variant names:

• chr11-65856268-A-G
• rs11227332
• ENST00000530413.1:c.-74T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CFL1	NM_005507.3	c.4-26T>C		intron_variant	Intron 1 of 3	ENST00000308162.10	NP_005498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10	c.4-26T>C		intron_variant	Intron 1 of 3	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

GnomAD2 exomes AF: 0.149 AC: 36637 AN: 245134 AF XY: 0.149

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 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

African (AFR) AF: 0.0686 AC: 2264 AN: 33008

American (AMR) AF: 0.131 AC: 5724 AN: 43836

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6166 AN: 25644

East Asian (EAS) AF: 0.0664 AC: 2619 AN: 39430

South Asian (SAS) AF: 0.0896 AC: 7646 AN: 85374

European-Finnish (FIN) AF: 0.150 AC: 7980 AN: 53086

Middle Eastern (MID) AF: 0.181 AC: 1036 AN: 5712

European-Non Finnish (NFE) AF: 0.191 AC: 210731 AN: 1101942

Other (OTH) AF: 0.165 AC: 9878 AN: 59730

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

African (AFR) AF: 0.0738 AC: 3064 AN: 41530

American (AMR) AF: 0.141 AC: 2156 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3472

East Asian (EAS) AF: 0.0654 AC: 339 AN: 5186

South Asian (SAS) AF: 0.0822 AC: 397 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1624 AN: 10600

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12862 AN: 67974

Other (OTH) AF: 0.155 AC: 327 AN: 2106

Alfa AF: 0.175 Hom.: 4785

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
PhyloP100		1.3
BranchPoint Hunter		6.0
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11227332; hg19: chr11-65623739; COSMIC: COSV107336991; COSMIC: COSV107336991;