rs36024

chr16-55672479-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.644+304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,070 control chromosomes in the GnomAD database, including 23,642 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 0.55 (23642 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.644+304A>G		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.644+304A>G		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84202 AN: 151952 Hom.: 23640 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.554 AC: 84239 AN: 152070 Hom.: 23642 Cov.: 32 AF XY: 0.558 AC XY: 41491 AN XY: 74346

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.564

Alfa AF: 0.581 Hom.: 35696

Bravo AF: 0.547

Asia WGS AF: 0.504 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.6
Dann	Benign	0.62

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: rs36024; hg19: chr16-55706391;