17-28886972-C-T

Variant names:

• chr17-28886972-C-T
• rs8081659
• NM_004475.3:c.131+1973G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004475.3(FLOT2):​c.131+1973G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,642 control chromosomes in the GnomAD database, including 12,658 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 0.38 (12658 hom., cov: 30)
• Consequence: FLOT2 NM_004475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 8 publications found

Genes affected

FLOT2 (HGNC:3758): (flotillin 2) Caveolae are small domains on the inner cell membrane involved in vesicular trafficking and signal transduction. This gene encodes a caveolae-associated, integral membrane protein, which is thought to function in neuronal signaling. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLOT2	NM_004475.3	c.131+1973G>A		intron_variant	Intron 2 of 10	ENST00000394908.9	NP_004466.2
FLOT2	NM_001330170.2	c.132-1025G>A		intron_variant	Intron 2 of 10		NP_001317099.1
FLOT2	XM_017024394.2	c.-17+1973G>A		intron_variant	Intron 2 of 10		XP_016879883.1
FLOT2	XM_024450667.2	c.-10+1973G>A		intron_variant	Intron 2 of 9		XP_024306435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLOT2	ENST00000394908.9	c.131+1973G>A		intron_variant	Intron 2 of 10	1	NM_004475.3	ENSP00000378368.3

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58103 AN: 151524 Hom.: 12656 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.383 AC: 58116 AN: 151642 Hom.: 12658 Cov.: 30 AF XY: 0.382 AC XY: 28270 AN XY: 74054

African (AFR) AF: 0.180 AC: 7452 AN: 41332

American (AMR) AF: 0.343 AC: 5219 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1417 AN: 5142

South Asian (SAS) AF: 0.473 AC: 2268 AN: 4798

European-Finnish (FIN) AF: 0.480 AC: 5034 AN: 10488

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33554 AN: 67882

Other (OTH) AF: 0.407 AC: 858 AN: 2108

Alfa AF: 0.463 Hom.: 32769

Bravo AF: 0.364

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		-0.24
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8081659; hg19: chr17-27213990;