rs652021

Variant names:

• chr11-65855876-G-A
• rs652021
• NM_005507.3:c.311+59C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.79).
• 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 rank	MANE	Protein	UniProt
CFL1	NM_005507.3	c.311+59C>T		intron_variant	Intron 2 of 3	ENST00000308162.10	NP_005498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFL1	ENST00000308162.10	c.311+59C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.249 AC: 8128 AN: 32586

American (AMR) AF: 0.375 AC: 16019 AN: 42740

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 14879 AN: 23480

East Asian (EAS) AF: 0.323 AC: 12668 AN: 39242

South Asian (SAS) AF: 0.634 AC: 50531 AN: 79730

European-Finnish (FIN) AF: 0.700 AC: 36315 AN: 51908

Middle Eastern (MID) AF: 0.702 AC: 3920 AN: 5584

European-Non Finnish (NFE) AF: 0.669 AC: 723067 AN: 1080656

Other (OTH) AF: 0.619 AC: 36115 AN: 58374

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

African (AFR) AF: 0.263 AC: 10893 AN: 41388

American (AMR) AF: 0.469 AC: 7160 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2218 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1632 AN: 5148

South Asian (SAS) AF: 0.620 AC: 2986 AN: 4816

European-Finnish (FIN) AF: 0.705 AC: 7418 AN: 10520

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45572 AN: 67906

Other (OTH) AF: 0.560 AC: 1175 AN: 2100

Alfa AF: 0.626 Hom.: 13801

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
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs652021; hg19: chr11-65623347; COSMIC: COSV108151663; COSMIC: COSV108151663;