chr17-30215370-T-A

Variant names:

• chr17-30215370-T-A
• rs717742
• NM_001045.6:c.1076+241A>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.1076+241A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,188 control chromosomes in the GnomAD database, including 40,038 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 0.70 (40038 hom., cov: 33)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 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.1076+241A>T		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.1076+241A>T		intron	N/A	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.1076+241A>T		intron	N/A	ENSP00000261707.3
	SLC6A4	ENST00000394821.2	TSL:1	c.1076+241A>T		intron	N/A	ENSP00000378298.2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106136 AN: 152070 Hom.: 40026 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.698 AC: 106172 AN: 152188 Hom.: 40038 Cov.: 33 AF XY: 0.703 AC XY: 52313 AN XY: 74404

African (AFR) AF: 0.376 AC: 15608 AN: 41474

American (AMR) AF: 0.801 AC: 12252 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3470

East Asian (EAS) AF: 0.903 AC: 4667 AN: 5166

South Asian (SAS) AF: 0.818 AC: 3951 AN: 4832

European-Finnish (FIN) AF: 0.819 AC: 8693 AN: 10610

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55507 AN: 68014

Other (OTH) AF: 0.731 AC: 1543 AN: 2112

Alfa AF: 0.740 Hom.: 5154

Bravo AF: 0.684

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.79
PhyloP100		0.66
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: rs717742; hg19: chr17-28542388;