17-30232164-G-T

Position:

• chr17-30232164-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1 BS2_Supporting

The NM_001045.6(SLC6A4):​c.-221+3449C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 152,268 control chromosomes in the GnomAD database, including 92 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 0.027 (92 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0275 (4184/152268) while in subpopulation NFE AF= 0.0341 (2322/68010). AF 95% confidence interval is 0.033. There are 92 homozygotes in gnomad4. There are 1963 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4184 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-221+3449C>A		intron_variant		ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.-221+3449C>A		intron_variant			NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-221+3449C>A		intron_variant		1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-221+3449C>A		intron_variant		1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-124+3449C>A		intron_variant		5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4189 AN: 152150 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0275 AC: 4184 AN: 152268 Hom.: 92 Cov.: 32 AF XY: 0.0264 AC XY: 1963 AN XY: 74448

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0120 Hom.: 1

Bravo AF: 0.0303

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.75

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: rs8073965; hg19: chr17-28559182;