17-30222960-G-T

Variant names:

• chr17-30222960-G-T
• rs25528
• NM_001045.6:c.-220-45C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001045.6(SLC6A4):​c.-220-45C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 685,978 control chromosomes in the GnomAD database, including 218,734 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 0.72 (41171 hom., cov: 32)
  • Exomes 𝑓: 0.81 (177563 hom.)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-220-45C>A		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.-220-45C>A		intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-220-45C>A		intron_variant	Intron 1 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-220-45C>A		intron_variant	Intron 1 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-123-879C>A		intron_variant	Intron 1 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109204 AN: 151934 Hom.: 41160 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.814 AC: 434431 AN: 533926 Hom.: 177563 Cov.: 7 AF XY: 0.814 AC XY: 228668 AN XY: 280788

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.830

Gnomad4 EAS exome AF: 0.880

Gnomad4 SAS exome AF: 0.816

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.718 AC: 109243 AN: 152052 Hom.: 41171 Cov.: 32 AF XY: 0.724 AC XY: 53763 AN XY: 74306

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.746

Alfa AF: 0.711 Hom.: 6613

Bravo AF: 0.708

Asia WGS AF: 0.811 AC: 2819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs25528; hg19: chr17-28549978; COSMIC: COSV55566423;