rs1610905

chr16-55657912-C-CTCCTGCGGTGCCCAGchr16-55657912-C-CTCCTGCGGTGCCCGGchr16-55657912-C-CTCCTGCGGTGCTCAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001172501.3(SLC6A2):c.274+950_274+951insGGTGCCCAGTCCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18729 hom., cov: 0)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.274+950_274+951insGGTGCCCAGTCCTGC		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.274+950_274+951insGGTGCCCAGTCCTGC		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74705 AN: 151704 Hom.: 18722 Cov.: 0

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.492 AC: 74747 AN: 151822 Hom.: 18729 Cov.: 0 AF XY: 0.499 AC XY: 37041 AN XY: 74174

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.509

Alfa AF: 0.328 Hom.: 665

Asia WGS AF: 0.474 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1610905; hg19: chr16-55691824;