16-55702000-C-T

Position:

• chr16-55702000-C-T

Variant summary

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

The NM_001172501.3(SLC6A2):​c.1830+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 1,231,124 control chromosomes in the GnomAD database, including 252,707 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 0.53 (24372 hom., cov: 33)
  • Exomes 𝑓: 0.64 (228335 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.1830+66C>T		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.1830+66C>T		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81002 AN: 151978 Hom.: 24362 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.643 AC: 693503 AN: 1079028 Hom.: 228335 AF XY: 0.638 AC XY: 353618 AN XY: 554154

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.533 AC: 81020 AN: 152096 Hom.: 24372 Cov.: 33 AF XY: 0.529 AC XY: 39345 AN XY: 74352

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.558

Alfa AF: 0.642 Hom.: 31871

Bravo AF: 0.528

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.80

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: rs2242447; hg19: chr16-55735912; COSMIC: COSV54920545; COSMIC: COSV54920545;