chr17-30223870-C-G

Variant names:

• chr17-30223870-C-G
• rs12150214
• NM_001045.6:c.-220-955G>C

Variant summary

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

The NM_001045.6(SLC6A4):​c.-220-955G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,834 control chromosomes in the GnomAD database, including 44,045 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 0.75 (44045 hom., cov: 30)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-220-955G>C		intron_variant	Intron 1 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.-220-955G>C		intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-220-955G>C		intron_variant	Intron 1 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-220-955G>C		intron_variant	Intron 1 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-123-1789G>C		intron_variant	Intron 1 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114426 AN: 151714 Hom.: 44032 Cov.: 30

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.754 AC: 114479 AN: 151834 Hom.: 44045 Cov.: 30 AF XY: 0.758 AC XY: 56203 AN XY: 74176

African (AFR) AF: 0.578 AC: 23899 AN: 41328

American (AMR) AF: 0.823 AC: 12545 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2888 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4611 AN: 5170

South Asian (SAS) AF: 0.822 AC: 3946 AN: 4802

European-Finnish (FIN) AF: 0.819 AC: 8637 AN: 10544

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55273 AN: 67960

Other (OTH) AF: 0.769 AC: 1620 AN: 2108

Alfa AF: 0.771 Hom.: 5366

Bravo AF: 0.748

Asia WGS AF: 0.823 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.48
DANN	Benign	0.42
PhyloP100		-0.56
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: rs12150214; hg19: chr17-28550888;