rs879519

chr16-55690499-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172501.3(SLC6A2):c.784-1419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,052 control chromosomes in the GnomAD database, including 17,339 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 0.47 (17339 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.784-1419A>G		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.784-1419A>G		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72147 AN: 151934 Hom.: 17328 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.475 AC: 72180 AN: 152052 Hom.: 17339 Cov.: 32 AF XY: 0.476 AC XY: 35398 AN XY: 74324

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.499

Alfa AF: 0.483 Hom.: 28411

Bravo AF: 0.477

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.072
Dann	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs879519; hg19: chr16-55724411;