chr17-30238543-A-G

Variant names:

• chr17-30238543-A-G
• rs4251416
• ENST00000577420.2:n.2A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000577420.2(ENSG00000266120):​n.2A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 151,924 control chromosomes in the GnomAD database, including 21 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 0.013 (21 hom., cov: 32)
• Consequence: ENSG00000266120 ENST00000577420.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 0 publications found

Genes affected

ENSG00000266120 (HGNC:):

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):

• obsessive-compulsive disorder

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• 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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0134 (2035/151924) while in subpopulation NFE AF = 0.0229 (1554/67910). AF 95% confidence interval is 0.0219. There are 21 homozygotes in GnomAd4. There are 933 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577420.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000266120	ENST00000577420.2	TSL:3	n.2A>G		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000266120	ENST00000724731.1		n.463A>G		non_coding_transcript_exon	Exon 3 of 5
	SLC6A4	ENST00000855095.1		c.-280T>C		upstream_gene	N/A	ENSP00000525154.1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2035 AN: 151806 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00375

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00649

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00500

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0134 AC: 2035 AN: 151924 Hom.: 21 Cov.: 32 AF XY: 0.0126 AC XY: 933 AN XY: 74276

African (AFR) AF: 0.00374 AC: 155 AN: 41440

American (AMR) AF: 0.00648 AC: 99 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00501 AC: 24 AN: 4792

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0229 AC: 1554 AN: 67910

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.0197 Hom.: 3

Bravo AF: 0.0126

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.90
DANN	Benign	0.26
PhyloP100		-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4251416; hg19: chr17-28565561; COSMIC: COSV55566301;