rs1532701

Variant names:

• chr16-55664115-G-A
• rs1532701
• NM_001172501.3:c.275-5450G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-55664115-G-A
• chr16-55664115-G-C

Variant summary

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

The NM_001172501.3(SLC6A2):​c.275-5450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,964 control chromosomes in the GnomAD database, including 21,600 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 0.53 (21600 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 9 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: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.275-5450G>A		intron_variant	Intron 2 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.275-5450G>A		intron_variant	Intron 2 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80807 AN: 151846 Hom.: 21587 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.532 AC: 80862 AN: 151964 Hom.: 21600 Cov.: 32 AF XY: 0.537 AC XY: 39844 AN XY: 74258

African (AFR) AF: 0.482 AC: 19964 AN: 41448

American (AMR) AF: 0.564 AC: 8616 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3101 AN: 5140

South Asian (SAS) AF: 0.605 AC: 2918 AN: 4824

European-Finnish (FIN) AF: 0.543 AC: 5725 AN: 10544

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36766 AN: 67948

Other (OTH) AF: 0.546 AC: 1154 AN: 2114

Alfa AF: 0.542 Hom.: 12732

Bravo AF: 0.532

Asia WGS AF: 0.582 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.29
PhyloP100		-0.61
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: rs1532701; hg19: chr16-55698027;