chr6-30729670-A-G

Variant names:

• chr6-30729670-A-G
• rs3094127
• NM_005803.4:c.1254+352T>C

Variant summary

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

The NM_005803.4(FLOT1):​c.1254+352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,086 control chromosomes in the GnomAD database, including 6,695 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 0.27 (6695 hom., cov: 32)
• Consequence: FLOT1 NM_005803.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 50 publications found

Genes affected

FLOT1 (HGNC:3757): (flotillin 1) This gene encodes an protein that localizes to the caveolae, which are small domains on the inner cell membranes. This protein plays a role in vesicle trafficking and cell morphology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005803.4. 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
	FLOT1	NM_005803.4	MANE Select	c.1254+352T>C		intron	N/A	NP_005794.1
	FLOT1	NM_001318875.2		c.1110+352T>C		intron	N/A	NP_001305804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLOT1	ENST00000376389.8	TSL:1 MANE Select	c.1254+352T>C		intron	N/A	ENSP00000365569.3
	FLOT1	ENST00000487376.5	TSL:5	n.1146+352T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40865 AN: 151968 Hom.: 6673 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.269 AC: 40921 AN: 152086 Hom.: 6695 Cov.: 32 AF XY: 0.259 AC XY: 19290 AN XY: 74360

African (AFR) AF: 0.460 AC: 19075 AN: 41446

American (AMR) AF: 0.224 AC: 3420 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1039 AN: 5190

South Asian (SAS) AF: 0.171 AC: 824 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1109 AN: 10606

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13978 AN: 67954

Other (OTH) AF: 0.278 AC: 585 AN: 2104

Alfa AF: 0.230 Hom.: 19427

Bravo AF: 0.290

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		1.6
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: rs3094127; hg19: chr6-30697447;