16-55697823-G-A

Position:

• chr16-55697823-G-A

Variant summary

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

The NM_001172501.3(SLC6A2):​c.1261-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,571,616 control chromosomes in the GnomAD database, including 26,358 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 0.19 (3094 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23264 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3	c.1261-74G>A		intron_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000568943.6	c.1261-74G>A		intron_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29167 AN: 151970 Hom.: 3083 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.177 AC: 251173 AN: 1419528 Hom.: 23264 AF XY: 0.176 AC XY: 124654 AN XY: 707288

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.0932

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.192 AC: 29215 AN: 152088 Hom.: 3094 Cov.: 32 AF XY: 0.189 AC XY: 14081 AN XY: 74352

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.187

Alfa AF: 0.172 Hom.: 3878

Bravo AF: 0.191

Asia WGS AF: 0.115 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.73

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: rs8047672; hg19: chr16-55731735; COSMIC: COSV54915968; COSMIC: COSV54915968;