16-55660998-G-C

Position:

• chr16-55660998-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001172501.3(SLC6A2):​c.274+4030G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,238 control chromosomes in the GnomAD database, including 765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (765 hom., cov: 33)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-55660998-G-C is Benign according to our data. Variant chr16-55660998-G-C is described in ClinVar as [Benign]. Clinvar id is 1251043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.274+4030G>C		intron_variant		ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.274+4030G>C		intron_variant		1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13651 AN: 152120 Hom.: 765 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0864

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

GnomAD4 genome AF: 0.0897 AC: 13663 AN: 152238 Hom.: 765 Cov.: 33 AF XY: 0.0908 AC XY: 6761 AN XY: 74444

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0855

Alfa AF: 0.0386 Hom.: 49

Bravo AF: 0.0799

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.43

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: rs12932949; hg19: chr16-55694910;