rs36020

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001172501.3(SLC6A2):​c.645-5967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,980 control chromosomes in the GnomAD database, including 1,082 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 0.11 ( 1082 hom., cov: 32)

Consequence

SLC6A2
NM_001172501.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.28
Variant links:
Genes affected
SLC6A2 (HGNC:11048): (solute carrier family 6 member 2) This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A2NM_001172501.3 linkc.645-5967C>T intron_variant Intron 4 of 14 ENST00000568943.6 NP_001165972.1 P23975-1A0A024R6T9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A2ENST00000568943.6 linkc.645-5967C>T intron_variant Intron 4 of 14 1 NM_001172501.3 ENSP00000457473.1 P23975-1

Frequencies

GnomAD3 genomes
AF:
0.114
AC:
17241
AN:
151886
Hom.:
1078
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0590
Gnomad AMI
AF:
0.0570
Gnomad AMR
AF:
0.101
Gnomad ASJ
AF:
0.133
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.0788
Gnomad FIN
AF:
0.168
Gnomad MID
AF:
0.173
Gnomad NFE
AF:
0.139
Gnomad OTH
AF:
0.120
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.114
AC:
17255
AN:
151980
Hom.:
1082
Cov.:
32
AF XY:
0.114
AC XY:
8432
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.0589
AC:
0.0589427
AN:
0.0589427
Gnomad4 AMR
AF:
0.101
AC:
0.101166
AN:
0.101166
Gnomad4 ASJ
AF:
0.133
AC:
0.133295
AN:
0.133295
Gnomad4 EAS
AF:
0.168
AC:
0.167825
AN:
0.167825
Gnomad4 SAS
AF:
0.0794
AC:
0.079375
AN:
0.079375
Gnomad4 FIN
AF:
0.168
AC:
0.167808
AN:
0.167808
Gnomad4 NFE
AF:
0.139
AC:
0.138571
AN:
0.138571
Gnomad4 OTH
AF:
0.124
AC:
0.124167
AN:
0.124167
Heterozygous variant carriers
0
790
1580
2370
3160
3950
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
200
400
600
800
1000
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.126
Hom.:
1871
Bravo
AF:
0.107
Asia WGS
AF:
0.130
AC:
452
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.075
DANN
Benign
0.21
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs36020; hg19: chr16-55713088; API