NM_005507.3:c.4-312A>G

Variant names:

• chr11-65856554-T-C
• rs665306
• NM_005507.3:c.4-312A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005507.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFL1	NM_005507.3	MANE Select	c.4-312A>G		intron	N/A	NP_005498.1	P23528

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFL1	ENST00000308162.10	TSL:1 MANE Select	c.4-312A>G		intron	N/A	ENSP00000309629.5	P23528
	CFL1	ENST00000534769.5	TSL:2	c.118-312A>G		intron	N/A	ENSP00000431696.1	E9PK25
	CFL1	ENST00000525451.6	TSL:2	c.4-312A>G		intron	N/A	ENSP00000432660.1	P23528

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

African (AFR) AF: 0.244 AC: 1337 AN: 5478

American (AMR) AF: 0.416 AC: 2643 AN: 6348

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 3089 AN: 5024

East Asian (EAS) AF: 0.302 AC: 2461 AN: 8146

South Asian (SAS) AF: 0.627 AC: 17963 AN: 28632

European-Finnish (FIN) AF: 0.687 AC: 6014 AN: 8750

Middle Eastern (MID) AF: 0.708 AC: 511 AN: 722

European-Non Finnish (NFE) AF: 0.665 AC: 69771 AN: 104906

Other (OTH) AF: 0.614 AC: 5928 AN: 9648

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

African (AFR) AF: 0.264 AC: 10970 AN: 41484

American (AMR) AF: 0.469 AC: 7169 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2218 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5166

South Asian (SAS) AF: 0.620 AC: 2989 AN: 4818

European-Finnish (FIN) AF: 0.706 AC: 7458 AN: 10560

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

European-Non Finnish (NFE) AF: 0.672 AC: 45694 AN: 67974

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.560 Hom.: 16083

Bravo AF: 0.493

Asia WGS AF: 0.489 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		-0.70
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs665306; hg19: chr11-65624025;