16-55672587-A-G

Variant names:

• chr16-55672587-A-G
• rs187714
• NM_001172501.3:c.644+412A>G

Variant summary

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

The NM_001172501.3(SLC6A2):​c.644+412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,986 control chromosomes in the GnomAD database, including 11,768 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 0.39 (11768 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.644+412A>G		intron_variant	Intron 4 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.644+412A>G		intron_variant	Intron 4 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58529 AN: 151868 Hom.: 11764 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.385 AC: 58550 AN: 151986 Hom.: 11768 Cov.: 32 AF XY: 0.390 AC XY: 28952 AN XY: 74286

African (AFR) AF: 0.265 AC: 11003 AN: 41470

American (AMR) AF: 0.447 AC: 6838 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2320 AN: 5130

South Asian (SAS) AF: 0.481 AC: 2317 AN: 4818

European-Finnish (FIN) AF: 0.412 AC: 4344 AN: 10546

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28772 AN: 67952

Other (OTH) AF: 0.409 AC: 861 AN: 2106

Alfa AF: 0.420 Hom.: 7292

Bravo AF: 0.384

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.045
DANN	Benign	0.67
PhyloP100		-1.5
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: rs187714; hg19: chr16-55706499;