17-30228407-G-C

Variant names:

• chr17-30228407-G-C
• rs16965628
• NM_001045.6:c.-220-5492C>G

Variant summary

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

The ENST00000261707.7(SLC6A4):​c.-220-5492C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,166 control chromosomes in the GnomAD database, including 2,507 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 0.14 (2507 hom., cov: 32)
• Consequence: SLC6A4 ENST00000261707.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-220-5492C>G		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.-220-5492C>G		intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-220-5492C>G		intron_variant	Intron 1 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-220-5492C>G		intron_variant	Intron 1 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-123-6326C>G		intron_variant	Intron 1 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20529 AN: 152048 Hom.: 2491 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0518

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.135 AC: 20593 AN: 152166 Hom.: 2507 Cov.: 32 AF XY: 0.133 AC XY: 9897 AN XY: 74408

African (AFR) AF: 0.318 AC: 13165 AN: 41450

American (AMR) AF: 0.0784 AC: 1198 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3472

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5184

South Asian (SAS) AF: 0.122 AC: 586 AN: 4820

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4349 AN: 68026

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.101 Hom.: 189

Bravo AF: 0.145

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-0.88
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

Publications

LitVar

Other links and lift over

dbSNP: rs16965628; hg19: chr17-28555425;