NM_001045.6:c.1651-1436G>A

Variant names:

• chr17-30204775-C-T
• rs3794808
• NM_001045.6:c.1651-1436G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001045.6(SLC6A4):​c.1651-1436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,052 control chromosomes in the GnomAD database, including 14,975 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 0.43 (14975 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 44 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.1651-1436G>A		intron	N/A	NP_001036.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.1651-1436G>A		intron	N/A	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.1651-1436G>A		intron	N/A	ENSP00000261707.3
	SLC6A4	ENST00000394821.2	TSL:1	c.1651-1436G>A		intron	N/A	ENSP00000378298.2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65787 AN: 151934 Hom.: 14977 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.433 AC: 65809 AN: 152052 Hom.: 14975 Cov.: 32 AF XY: 0.441 AC XY: 32743 AN XY: 74314

African (AFR) AF: 0.365 AC: 15117 AN: 41460

American (AMR) AF: 0.511 AC: 7803 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4229 AN: 5184

South Asian (SAS) AF: 0.488 AC: 2350 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4273 AN: 10558

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28606 AN: 67964

Other (OTH) AF: 0.462 AC: 976 AN: 2114

Alfa AF: 0.434 Hom.: 15852

Bravo AF: 0.442

Asia WGS AF: 0.571 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.47
PhyloP100		1.1
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: rs3794808; hg19: chr17-28531793;