rs2054847

Variant names:

• chr17-30204995-G-A
• rs2054847
• NM_001045.6:c.1651-1656C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-30204995-G-A
• chr17-30204995-G-C
• chr17-30204995-G-T

Variant summary

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

The NM_001045.6(SLC6A4):​c.1651-1656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,988 control chromosomes in the GnomAD database, including 12,162 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 0.36 (12162 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 20 publications found

Genes affected

SLC6A4 (HGNC:11050): (solute carrier family 6 member 4) This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]

SLC6A4 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LOC124903970 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.1651-1656C>T		intron	N/A	NP_001036.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.1651-1656C>T		intron	N/A	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.1651-1656C>T		intron	N/A	ENSP00000261707.3
	SLC6A4	ENST00000394821.2	TSL:1	c.1651-1656C>T		intron	N/A	ENSP00000378298.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54530 AN: 151870 Hom.: 12167 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.359 AC: 54515 AN: 151988 Hom.: 12162 Cov.: 31 AF XY: 0.368 AC XY: 27372 AN XY: 74284

African (AFR) AF: 0.112 AC: 4623 AN: 41454

American (AMR) AF: 0.483 AC: 7376 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3470

East Asian (EAS) AF: 0.817 AC: 4217 AN: 5164

South Asian (SAS) AF: 0.484 AC: 2335 AN: 4822

European-Finnish (FIN) AF: 0.401 AC: 4225 AN: 10532

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28458 AN: 67976

Other (OTH) AF: 0.401 AC: 842 AN: 2098

Alfa AF: 0.409 Hom.: 5806

Bravo AF: 0.358

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-0.14
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: rs2054847; hg19: chr17-28532013;