NM_004475.3:c.915-196C>T

Variant names:

• chr17-28881571-G-A
• rs3816848
• NM_004475.3:c.915-196C>T

Variant summary

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

The NM_004475.3(FLOT2):​c.915-196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,178 control chromosomes in the GnomAD database, including 28,014 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 0.57 (28014 hom., cov: 34)
• Consequence: FLOT2 NM_004475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLOT2	NM_004475.3	MANE Select	c.915-196C>T		intron	N/A	NP_004466.2
	FLOT2	NM_001330170.2		c.915-196C>T		intron	N/A	NP_001317099.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLOT2	ENST00000394908.9	TSL:1 MANE Select	c.915-196C>T		intron	N/A	ENSP00000378368.3
	FLOT2	ENST00000394906.6	TSL:5	c.1080-196C>T		intron	N/A	ENSP00000378366.2
	FLOT2	ENST00000585169.6	TSL:5	c.915-196C>T		intron	N/A	ENSP00000463503.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87301 AN: 152060 Hom.: 28008 Cov.: 34

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.574 AC: 87321 AN: 152178 Hom.: 28014 Cov.: 34 AF XY: 0.576 AC XY: 42827 AN XY: 74390

African (AFR) AF: 0.264 AC: 10984 AN: 41530

American (AMR) AF: 0.605 AC: 9251 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2508 AN: 3466

East Asian (EAS) AF: 0.702 AC: 3620 AN: 5160

South Asian (SAS) AF: 0.730 AC: 3526 AN: 4828

European-Finnish (FIN) AF: 0.685 AC: 7254 AN: 10594

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48193 AN: 67990

Other (OTH) AF: 0.611 AC: 1287 AN: 2108

Alfa AF: 0.671 Hom.: 16997

Bravo AF: 0.558

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.83
PhyloP100		-0.022
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3816848; hg19: chr17-27208589;