rs8081028

Variant names:

• chr17-30196296-C-A
• rs8081028
• NM_001045.6:c.*2160G>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.*2160G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 149,262 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (372 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42
• Publications: 2 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=-0.93).
• BP6: Variant 17-30196296-C-A is Benign according to our data. Variant chr17-30196296-C-A is described in ClinVar as Benign. ClinVar VariationId is 891374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 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.*2160G>T		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.*2160G>T		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.*2160G>T		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000401766.6	TSL:5	c.*2160G>T		3_prime_UTR	Exon 14 of 14	ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8045 AN: 149134 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0243

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.0500 AC: 2 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 2 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0526 AC: 2 AN: 38

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0540 AC: 8065 AN: 149222 Hom.: 372 Cov.: 32 AF XY: 0.0527 AC XY: 3840 AN XY: 72804

African (AFR) AF: 0.130 AC: 5286 AN: 40774

American (AMR) AF: 0.0332 AC: 500 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.0243 AC: 84 AN: 3454

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5144

South Asian (SAS) AF: 0.0224 AC: 106 AN: 4742

European-Finnish (FIN) AF: 0.0110 AC: 105 AN: 9562

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0275 AC: 1850 AN: 67210

Other (OTH) AF: 0.0487 AC: 101 AN: 2072

Alfa AF: 0.0385 Hom.: 220

Bravo AF: 0.0585

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.93
CADD	Benign	0.78
DANN	Benign	0.39
PhyloP100		-2.4
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: rs8081028; hg19: chr17-28523314;