rs2071242

Positions:

• chr17-18251196-T-C

Variant summary

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

The NM_002018.4(FLII):​c.1596+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,535,390 control chromosomes in the GnomAD database, including 42,476 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 0.22 (3883 hom., cov: 33)
  • Exomes 𝑓: 0.23 (38593 hom.)
• Consequence: FLII NM_002018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

Genes affected

FLII (HGNC:3750): (FLII actin remodeling protein) This gene encodes a protein with a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat-protein protein interaction domain. The protein is similar to a Drosophila protein involved in early embryogenesis and the structural organization of indirect flight muscle. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLII	NM_002018.4	c.1596+69A>G		intron_variant		ENST00000327031.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLII	ENST00000327031.9	c.1596+69A>G		intron_variant		1	NM_002018.4	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33450 AN: 151994 Hom.: 3876 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.234 AC: 324379 AN: 1383278 Hom.: 38593 Cov.: 24 AF XY: 0.234 AC XY: 160074 AN XY: 685162

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.220 AC: 33476 AN: 152112 Hom.: 3883 Cov.: 33 AF XY: 0.219 AC XY: 16295 AN XY: 74354

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.223

Alfa AF: 0.241 Hom.: 4347

Bravo AF: 0.220

Asia WGS AF: 0.207 AC: 719 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071242; hg19: chr17-18154510; COSMIC: COSV58944804; COSMIC: COSV58944804;