rs3813034

Variant names:

• chr17-30197786-A-C
• rs3813034
• NM_001045.6:c.*670T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-30197786-A-C
• chr17-30197786-A-G
• chr17-30197786-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 69 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):

• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045.6. 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
	SLC6A4	NM_001045.6	MANE Select	c.*670T>G		3_prime_UTR	Exon 15 of 15	NP_001036.1	P31645-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.*670T>G		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.*670T>G		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000401766.6	TSL:5	c.*670T>G		3_prime_UTR	Exon 14 of 14	ENSP00000385822.2	P31645-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.348 AC: 48 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.425 AC: 113 AN: 266

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.563 AC: 9 AN: 16

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.228 AC: 9465 AN: 41490

American (AMR) AF: 0.504 AC: 7703 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4205 AN: 5160

South Asian (SAS) AF: 0.532 AC: 2564 AN: 4820

European-Finnish (FIN) AF: 0.439 AC: 4638 AN: 10576

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30655 AN: 67956

Other (OTH) AF: 0.443 AC: 935 AN: 2112

Alfa AF: 0.449 Hom.: 39366

Bravo AF: 0.413

Asia WGS AF: 0.582 AC: 2023 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Behavior disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.77
Mutation Taster		=100/0	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: rs3813034; hg19: chr17-28524804;