rs41154

Variant names:

• chr16-55668794-A-G
• rs41154
• NM_001172501.3:c.275-771A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-55668794-A-G
• chr16-55668794-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172501.3(SLC6A2):​c.275-771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,038 control chromosomes in the GnomAD database, including 11,377 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 0.38 (11377 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 3 publications found

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]

SLC6A2 Gene-Disease associations (from GenCC):

• postural orthostatic tachycardia syndrome

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.275-771A>G		intron_variant	Intron 2 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.275-771A>G		intron_variant	Intron 2 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57528 AN: 151920 Hom.: 11374 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.379 AC: 57547 AN: 152038 Hom.: 11377 Cov.: 32 AF XY: 0.383 AC XY: 28497 AN XY: 74328

African (AFR) AF: 0.260 AC: 10794 AN: 41474

American (AMR) AF: 0.443 AC: 6769 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1442 AN: 3472

East Asian (EAS) AF: 0.454 AC: 2345 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2233 AN: 4812

European-Finnish (FIN) AF: 0.411 AC: 4348 AN: 10568

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28152 AN: 67960

Other (OTH) AF: 0.400 AC: 843 AN: 2106

Alfa AF: 0.403 Hom.: 33894

Bravo AF: 0.378

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41154; hg19: chr16-55702706;