chr17-30235874-A-G

Variant names:

• chr17-30235874-A-G
• rs25533
• ENST00000261707.7:c.-482T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

SLC6A4 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261707.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.-482T>C		upstream_gene	N/A	NP_001036.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000261707.7	TSL:1	c.-482T>C		5_prime_UTR	Exon 1 of 15	ENSP00000261707.3
	SLC6A4	ENST00000401766.6	TSL:5	c.-385T>C		5_prime_UTR	Exon 1 of 14	ENSP00000385822.2
	SLC6A4	ENST00000650711.1	MANE Select	c.-482T>C		upstream_gene	N/A	ENSP00000498537.1

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.125 AC: 3 AN: 24

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0556 AC: 1 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0849 AC: 9 AN: 106

Other (OTH) AF: 0.00 AC: 0 AN: 8

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

African (AFR) AF: 0.0926 AC: 3846 AN: 41530

American (AMR) AF: 0.0415 AC: 636 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3470

East Asian (EAS) AF: 0.122 AC: 627 AN: 5156

South Asian (SAS) AF: 0.0693 AC: 334 AN: 4822

European-Finnish (FIN) AF: 0.0825 AC: 876 AN: 10614

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0712 AC: 4842 AN: 67988

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		-1.9
PromoterAI		0.063	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs25533; hg19: chr17-28562892;