dbSNP rs10521330: ENSG00000278928:n.2124A>G (chr16-55706242-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000682050.1(SLC6A2):n.*4449A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,176 control chromosomes in the GnomAD database, including 2,708 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 0.18 ( 2708 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

SLC6A2
ENST00000682050.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

4 publications found

Variant links:

Genes affected

ENSG00000278928 (HGNC:):

ENSG00000278928 links:

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, PanelApp Australia

SLC6A2 links:

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new If you want to explore the variant's impact on the transcript ENST00000682050.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682050.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	NM_001172501.3	MANE Select	c.*3896A>G		downstream_gene	N/A	NP_001165972.1	P23975-1
	SLC6A2	NM_001172504.1		c.*970A>G		downstream_gene	N/A	NP_001165975.1	P23975-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000278928	ENST00000624017.1	TSL:6	n.2124A>G	non_coding_transcript_exon	Exon 1 of 1
SLC6A2	ENST00000682050.1		n.*4449A>G	non_coding_transcript_exon	Exon 13 of 13	ENSP00000508367.1	A0A804HLI4
SLC6A2	ENST00000682050.1		n.*4449A>G	3_prime_UTR	Exon 13 of 13	ENSP00000508367.1	A0A804HLI4

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27706

AN:

152058

Hom.:

2702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0308

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.182

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.182

AC:

27747

AN:

152176

Hom.:

2708

Cov.:

AF XY:

0.183

AC XY:

13580

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.250

AC:

10384

AN:

41502

American (AMR)

AF:

0.124

AC:

1891

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3468

East Asian (EAS)

AF:

0.0309

AC:

160

AN:

5180

South Asian (SAS)

AF:

0.201

AC:

972

AN:

4826

European-Finnish (FIN)

AF:

0.194

AC:

2049

AN:

10588

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11086

AN:

67998

Other (OTH)

AF:

0.180

AC:

381

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1155

2310

3466

4621

5776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.158

Hom.:

2991

Bravo

AF:

0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.067

(source)

DANN

Benign

0.65

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over