rs40434

chr16-55665613-A-Gchr16-55665613-A-T

Variant summary

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

The NM_001172501.3(SLC6A2):c.275-3952A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,786 control chromosomes in the GnomAD database, including 9,224 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 0.31 (9224 hom., cov: 31)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.275-3952A>G		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.275-3952A>G		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47737 AN: 151668 Hom.: 9221 Cov.: 31

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.315 AC: 47740 AN: 151786 Hom.: 9224 Cov.: 31 AF XY: 0.318 AC XY: 23609 AN XY: 74172

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.348

Alfa AF: 0.352 Hom.: 1281

Bravo AF: 0.307

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.7
Dann	Benign	0.69

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: rs40434; hg19: chr16-55699525;