11-65827349-T-C

Variant names:

• chr11-65827349-T-C
• rs7102454
• XM_047427976.1:c.*598-740A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047427976.1(LOC124902693):​c.*598-740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,144 control chromosomes in the GnomAD database, including 6,260 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 0.28 (6260 hom., cov: 33)
• Consequence: LOC124902693 XM_047427976.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 24 publications found

Genes affected

LOC124902693 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525710.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFL1	ENST00000525710.1	TSL:5	n.474-740A>G		intron	N/A
	CFL1	ENST00000527752.1	TSL:5	n.62-740A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42503 AN: 152026 Hom.: 6247 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42551 AN: 152144 Hom.: 6260 Cov.: 33 AF XY: 0.272 AC XY: 20219 AN XY: 74392

African (AFR) AF: 0.204 AC: 8460 AN: 41528

American (AMR) AF: 0.257 AC: 3931 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1057 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1554 AN: 5184

South Asian (SAS) AF: 0.128 AC: 619 AN: 4828

European-Finnish (FIN) AF: 0.260 AC: 2750 AN: 10580

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.342 AC: 23232 AN: 67966

Other (OTH) AF: 0.283 AC: 595 AN: 2104

Alfa AF: 0.321 Hom.: 30370

Bravo AF: 0.279

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.47
PhyloP100		-0.099

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7102454; hg19: chr11-65594820;