17-30235874-A-G

Position:

• chr17-30235874-A-G

Variant summary

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

The ENST00000261707.7(SLC6A4):​c.-482T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,376 control chromosomes in the GnomAD database, including 450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (450 hom., cov: 32)
  • Exomes 𝑓: 0.077 (0 hom.)
• Consequence: SLC6A4 ENST00000261707.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85

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=-0.8).
• BP6: Variant 17-30235874-A-G is Benign according to our data. Variant chr17-30235874-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 322550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000261707.7	c.-482T>C		5_prime_UTR_variant	1/15	1		ENSP00000261707	P1
SLC6A4	ENST00000401766.6	c.-385T>C		5_prime_UTR_variant	1/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11467 AN: 152090 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0774 AC: 13 AN: 168 Hom.: 0 Cov.: 0 AF XY: 0.0814 AC XY: 7 AN XY: 86

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0849

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0754 AC: 11470 AN: 152208 Hom.: 450 Cov.: 32 AF XY: 0.0745 AC XY: 5548 AN XY: 74422

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.0825

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.193 Hom.: 1409

Bravo AF: 0.0714

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Behavior disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely 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	-0.80
CADD	Benign	1.6
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: rs25533; hg19: chr17-28562892;