17-30219328-C-T

Variant names:

• chr17-30219328-C-T
• rs1872924
• NM_001045.6:c.344-397G>A

Variant summary

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

The NM_001045.6(SLC6A4):​c.344-397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,978 control chromosomes in the GnomAD database, including 37,263 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 0.67 (37263 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.344-397G>A		intron_variant	Intron 3 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.344-397G>A		intron_variant	Intron 3 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.344-397G>A		intron_variant	Intron 3 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.344-397G>A		intron_variant	Intron 3 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.344-397G>A		intron_variant	Intron 2 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102136 AN: 151860 Hom.: 37248 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.672 AC: 102177 AN: 151978 Hom.: 37263 Cov.: 31 AF XY: 0.678 AC XY: 50393 AN XY: 74280

African (AFR) AF: 0.357 AC: 14786 AN: 41398

American (AMR) AF: 0.783 AC: 11949 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2831 AN: 3470

East Asian (EAS) AF: 0.889 AC: 4590 AN: 5164

South Asian (SAS) AF: 0.812 AC: 3911 AN: 4814

European-Finnish (FIN) AF: 0.778 AC: 8226 AN: 10570

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53507 AN: 67980

Other (OTH) AF: 0.706 AC: 1489 AN: 2110

Alfa AF: 0.716 Hom.: 5053

Bravo AF: 0.658

Asia WGS AF: 0.802 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.84
PhyloP100		1.4
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: rs1872924; hg19: chr17-28546346;