rs4564560

chr16-55690852-A-Gchr16-55690852-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.784-1066A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,010 control chromosomes in the GnomAD database, including 16,126 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 0.45 (16126 hom., cov: 31)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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.784-1066A>G		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.784-1066A>G		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68920 AN: 151892 Hom.: 16121 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.454 AC: 68943 AN: 152010 Hom.: 16126 Cov.: 31 AF XY: 0.456 AC XY: 33875 AN XY: 74298

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.486

Alfa AF: 0.475 Hom.: 9162

Bravo AF: 0.453

Asia WGS AF: 0.602 AC: 2093 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	0.028
Dann	Benign	0.72

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: rs4564560; hg19: chr16-55724764;