17-30197786-A-C

Position:

• chr17-30197786-A-C

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.*670T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,492 control chromosomes in the GnomAD database, including 14,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14378 hom., cov: 32)
  • Exomes 𝑓: 0.41 (37 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.770

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=-0.66).
• BP6: Variant 17-30197786-A-C is Benign according to our data. Variant chr17-30197786-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 322518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*670T>G		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.*670T>G		3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.*670T>G		3_prime_UTR_variant	15/15	1		ENSP00000261707	P1
SLC6A4	ENST00000401766.6	c.*670T>G		3_prime_UTR_variant	14/14	5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62626 AN: 151950 Hom.: 14381 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.406 AC: 172 AN: 424 Hom.: 37 Cov.: 0 AF XY: 0.410 AC XY: 105 AN XY: 256

Gnomad4 EAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.412 AC: 62625 AN: 152068 Hom.: 14378 Cov.: 32 AF XY: 0.420 AC XY: 31235 AN XY: 74348

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.443

Alfa AF: 0.449 Hom.: 14679

Bravo AF: 0.413

Asia WGS AF: 0.582 AC: 2023 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	-0.66
CADD	Benign	12
DANN	Benign	0.74

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: rs3813034; hg19: chr17-28524804;