17-30196296-C-A

Position:

• chr17-30196296-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001045.6(SLC6A4):​c.*2160G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 149,262 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (372 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-30196296-C-A is Benign according to our data. Variant chr17-30196296-C-A is described in ClinVar as [Benign]. Clinvar id is 891374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*2160G>T		3_prime_UTR_variant	15/15	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.*2160G>T		3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.*2160G>T		3_prime_UTR_variant	15/15	1		ENSP00000261707	P1
SLC6A4	ENST00000401766.6	c.*2160G>T		3_prime_UTR_variant	14/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8045 AN: 149134 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.0500 AC: 2 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 2 AN XY: 24

Gnomad4 EAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0540 AC: 8065 AN: 149222 Hom.: 372 Cov.: 32 AF XY: 0.0527 AC XY: 3840 AN XY: 72804

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0243

Gnomad4 EAS AF: 0.00214

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0347 Hom.: 126

Bravo AF: 0.0585

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Behavior disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.78
DANN	Benign	0.39

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: rs8081028; hg19: chr17-28523314;