rs2071242

Variant names:

• chr17-18251196-T-C
• rs2071242
• NM_002018.4:c.1596+69A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

FLII Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• cardiomyopathy, dilated, 2j

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002018.4. 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
	FLII	NM_002018.4	MANE Select	c.1596+69A>G		intron	N/A	NP_002009.1	Q13045-1
	FLII	NM_001256264.2		c.1563+69A>G		intron	N/A	NP_001243193.1	Q13045-3
	FLII	NM_001256265.2		c.1431+69A>G		intron	N/A	NP_001243194.1	Q13045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLII	ENST00000327031.9	TSL:1 MANE Select	c.1596+69A>G		intron	N/A	ENSP00000324573.4	Q13045-1
	FLII	ENST00000579294.5	TSL:1	c.1563+69A>G		intron	N/A	ENSP00000463534.1	Q13045-3
	FLII	ENST00000855814.1		c.1596+69A>G		intron	N/A	ENSP00000525873.1

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

African (AFR) AF: 0.152 AC: 4846 AN: 31812

American (AMR) AF: 0.247 AC: 10121 AN: 40942

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6375 AN: 23660

East Asian (EAS) AF: 0.262 AC: 10041 AN: 38346

South Asian (SAS) AF: 0.192 AC: 15278 AN: 79724

European-Finnish (FIN) AF: 0.261 AC: 13297 AN: 50914

Middle Eastern (MID) AF: 0.280 AC: 1560 AN: 5580

European-Non Finnish (NFE) AF: 0.236 AC: 249310 AN: 1054972

Other (OTH) AF: 0.236 AC: 13551 AN: 57328

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

African (AFR) AF: 0.155 AC: 6432 AN: 41508

American (AMR) AF: 0.240 AC: 3669 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1592 AN: 5160

South Asian (SAS) AF: 0.182 AC: 878 AN: 4816

European-Finnish (FIN) AF: 0.275 AC: 2913 AN: 10576

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16403 AN: 67980

Other (OTH) AF: 0.223 AC: 470 AN: 2108

Alfa AF: 0.237 Hom.: 5559

Bravo AF: 0.220

Asia WGS AF: 0.207 AC: 719 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.50
PhyloP100		-2.2
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: rs2071242; hg19: chr17-18154510; COSMIC: COSV58944804; COSMIC: COSV58944804;