chr16-55696212-A-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001172501.3(SLC6A2):​c.1148-13A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,504,612 control chromosomes in the GnomAD database, including 81,975 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 0.28 ( 6631 hom., cov: 32)
Exomes 𝑓: 0.33 ( 75344 hom. )

Consequence

SLC6A2
NM_001172501.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.843

Publications

26 publications found
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]
SLC6A2 Gene-Disease associations (from GenCC):
  • postural orthostatic tachycardia syndrome
    Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A2NM_001172501.3 linkc.1148-13A>C intron_variant Intron 8 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.1148-13A>C intron_variant Intron 8 of 14 1 NM_001172501.3 ENSP00000457473.1 P23975-1

Frequencies

GnomAD3 genomes
AF:
0.276
AC:
41893
AN:
151962
Hom.:
6629
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.365
Gnomad AMR
AF:
0.329
Gnomad ASJ
AF:
0.386
Gnomad EAS
AF:
0.285
Gnomad SAS
AF:
0.333
Gnomad FIN
AF:
0.360
Gnomad MID
AF:
0.348
Gnomad NFE
AF:
0.340
Gnomad OTH
AF:
0.290
GnomAD2 exomes
AF:
0.320
AC:
80507
AN:
251196
AF XY:
0.326
show subpopulations
Gnomad AFR exome
AF:
0.106
Gnomad AMR exome
AF:
0.325
Gnomad ASJ exome
AF:
0.389
Gnomad EAS exome
AF:
0.275
Gnomad FIN exome
AF:
0.358
Gnomad NFE exome
AF:
0.339
Gnomad OTH exome
AF:
0.341
GnomAD4 exome
AF:
0.329
AC:
445113
AN:
1352532
Hom.:
75344
Cov.:
21
AF XY:
0.331
AC XY:
224874
AN XY:
679308
show subpopulations
African (AFR)
AF:
0.102
AC:
3187
AN:
31358
American (AMR)
AF:
0.326
AC:
14544
AN:
44572
Ashkenazi Jewish (ASJ)
AF:
0.393
AC:
10019
AN:
25474
East Asian (EAS)
AF:
0.313
AC:
12282
AN:
39200
South Asian (SAS)
AF:
0.333
AC:
27945
AN:
84042
European-Finnish (FIN)
AF:
0.359
AC:
19139
AN:
53378
Middle Eastern (MID)
AF:
0.362
AC:
2012
AN:
5552
European-Non Finnish (NFE)
AF:
0.334
AC:
337923
AN:
1012282
Other (OTH)
AF:
0.319
AC:
18062
AN:
56674
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
15089
30178
45267
60356
75445
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10350
20700
31050
41400
51750
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.276
AC:
41903
AN:
152080
Hom.:
6631
Cov.:
32
AF XY:
0.277
AC XY:
20614
AN XY:
74334
show subpopulations
African (AFR)
AF:
0.108
AC:
4480
AN:
41510
American (AMR)
AF:
0.329
AC:
5036
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.386
AC:
1339
AN:
3468
East Asian (EAS)
AF:
0.285
AC:
1476
AN:
5174
South Asian (SAS)
AF:
0.333
AC:
1603
AN:
4820
European-Finnish (FIN)
AF:
0.360
AC:
3806
AN:
10564
Middle Eastern (MID)
AF:
0.347
AC:
102
AN:
294
European-Non Finnish (NFE)
AF:
0.340
AC:
23105
AN:
67940
Other (OTH)
AF:
0.296
AC:
624
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1540
3080
4621
6161
7701
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
426
852
1278
1704
2130
<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:
0.324
Hom.:
28995
Bravo
AF:
0.267
Asia WGS
AF:
0.292
AC:
1015
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
6.1
DANN
Benign
0.87
PhyloP100
-0.84
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

Other links and lift over

dbSNP: rs5568; hg19: chr16-55730124; COSMIC: COSV54915651; COSMIC: COSV54915651; API