rs187715

Variant names:

• chr16-55670130-T-C
• rs187715
• NM_001172501.3:c.406+434T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-55670130-T-C
• chr16-55670130-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001172501.3(SLC6A2):​c.406+434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,306 control chromosomes in the GnomAD database, including 134 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 0.036 (134 hom., cov: 33)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 4 publications found

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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.036 (5476/152306) while in subpopulation NFE AF = 0.0509 (3465/68014). AF 95% confidence interval is 0.0495. There are 134 homozygotes in GnomAd4. There are 2716 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5476 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172501.3. 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.406+434T>C		intron	N/A	NP_001165972.1	P23975-1
	SLC6A2	NM_001172504.1		c.406+434T>C		intron	N/A	NP_001165975.1	P23975-2
	SLC6A2	NM_001043.3		c.406+434T>C		intron	N/A	NP_001034.1	P23975-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000568943.6	TSL:1 MANE Select	c.406+434T>C		intron	N/A	ENSP00000457473.1	P23975-1
	SLC6A2	ENST00000379906.6	TSL:1	c.406+434T>C		intron	N/A	ENSP00000369237.2	P23975-1
	SLC6A2	ENST00000219833.13	TSL:5	c.406+434T>C		intron	N/A	ENSP00000219833.8	P23975-2

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5478 AN: 152188 Hom.: 134 Cov.: 33

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0360 AC: 5476 AN: 152306 Hom.: 134 Cov.: 33 AF XY: 0.0365 AC XY: 2716 AN XY: 74464

African (AFR) AF: 0.00960 AC: 399 AN: 41580

American (AMR) AF: 0.0345 AC: 528 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4830

European-Finnish (FIN) AF: 0.0655 AC: 695 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3465 AN: 68014

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0435 Hom.: 520

Bravo AF: 0.0321

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs187715; hg19: chr16-55704042;