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):

• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.*670T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.*670T>G		3_prime_UTR_variant	Exon 15 of 15		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.*670T>G		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000261707.3
SLC6A4	ENST00000401766.6	c.*670T>G		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000385822.2
SLC6A4	ENST00000579221.5	n.*987T>G		downstream_gene_variant		1		ENSP00000463172.1

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

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 v4.3

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;