rs10521330

chr16-55706242-A-Gchr16-55706242-A-T

Variant summary

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

The ENST00000624017.1(ENSG00000278928):n.2124A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,176 control chromosomes in the GnomAD database, including 2,708 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 0.18 (2708 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENST00000624017.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

Genes affected

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A2	NM_001172501.3			downstream_gene_variant		ENST00000568943.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000624017.1	n.2124A>G		non_coding_transcript_exon_variant	1/1
SLC6A2	ENST00000568943.6			downstream_gene_variant		1	NM_001172501.3	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27706 AN: 152058 Hom.: 2702 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.182

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.182 AC: 27747 AN: 152176 Hom.: 2708 Cov.: 32 AF XY: 0.183 AC XY: 13580 AN XY: 74376

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.180

Alfa AF: 0.154 Hom.: 2220

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.067
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521330; hg19: chr16-55740154;