NM_004475.3:c.*459C>T

Variant names:

• chr17-28880102-G-A
• rs10205
• NM_004475.3:c.*459C>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.*459C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,007,476 control chromosomes in the GnomAD database, including 54,182 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 0.41 (15859 hom., cov: 32)
  • Exomes 𝑓: 0.29 (38323 hom.)
• Consequence: FLOT2 NM_004475.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLOT2	NM_004475.3	c.*459C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000394908.9	NP_004466.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLOT2	ENST00000394908.9	c.*459C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_004475.3	ENSP00000378368.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62184 AN: 151960 Hom.: 15813 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.292 AC: 249525 AN: 855398 Hom.: 38323 Cov.: 32 AF XY: 0.290 AC XY: 114983 AN XY: 396734

African (AFR) AF: 0.766 AC: 12308 AN: 16058

American (AMR) AF: 0.242 AC: 791 AN: 3270

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 1463 AN: 5578

East Asian (EAS) AF: 0.188 AC: 831 AN: 4420

South Asian (SAS) AF: 0.257 AC: 5066 AN: 19696

European-Finnish (FIN) AF: 0.225 AC: 237 AN: 1052

Middle Eastern (MID) AF: 0.353 AC: 601 AN: 1702

European-Non Finnish (NFE) AF: 0.283 AC: 219784 AN: 775290

Other (OTH) AF: 0.298 AC: 8444 AN: 28332

GnomAD4 genome AF: 0.410 AC: 62280 AN: 152078 Hom.: 15859 Cov.: 32 AF XY: 0.406 AC XY: 30157 AN XY: 74350

African (AFR) AF: 0.731 AC: 30310 AN: 41464

American (AMR) AF: 0.299 AC: 4572 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1024 AN: 5154

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3324 AN: 10574

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19555 AN: 67986

Other (OTH) AF: 0.378 AC: 796 AN: 2108

Alfa AF: 0.382 Hom.: 2188

Bravo AF: 0.419

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.30
PhyloP100		-0.97
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: rs10205; hg19: chr17-27207120; COSMIC: COSV67529255; COSMIC: COSV67529255;