17-30196708-G-T

Variant names:

• chr17-30196708-G-T
• rs7224199
• NM_001045.6:c.*1748C>A

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.*1748C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,166 control chromosomes in the GnomAD database, including 19,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19298 hom., cov: 32)
  • Exomes 𝑓: 0.36 (11 hom.)
• Consequence: SLC6A4 NM_001045.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.498
• Publications: 33 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=-0.95).
• BP6: Variant 17-30196708-G-T is Benign according to our data. Variant chr17-30196708-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 322509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.*1748C>A		3_prime_UTR	Exon 15 of 15	NP_001036.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.*1748C>A		3_prime_UTR	Exon 15 of 15	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.*1748C>A		3_prime_UTR	Exon 15 of 15	ENSP00000261707.3
	SLC6A4	ENST00000401766.6	TSL:5	c.*1748C>A		3_prime_UTR	Exon 14 of 14	ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75454 AN: 151902 Hom.: 19293 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.356 AC: 52 AN: 146 Hom.: 11 Cov.: 0 AF XY: 0.354 AC XY: 29 AN XY: 82

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.346 AC: 47 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.497 AC: 75480 AN: 152020 Hom.: 19298 Cov.: 32 AF XY: 0.501 AC XY: 37261 AN XY: 74332

African (AFR) AF: 0.514 AC: 21306 AN: 41466

American (AMR) AF: 0.541 AC: 8253 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1941 AN: 3466

East Asian (EAS) AF: 0.815 AC: 4228 AN: 5186

South Asian (SAS) AF: 0.533 AC: 2572 AN: 4826

European-Finnish (FIN) AF: 0.439 AC: 4637 AN: 10570

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30893 AN: 67932

Other (OTH) AF: 0.509 AC: 1076 AN: 2112

Alfa AF: 0.480 Hom.: 27315

Bravo AF: 0.508

Asia WGS AF: 0.607 AC: 2113 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	-0.95
CADD	Benign	0.33
DANN	Benign	0.67
PhyloP100		-0.50
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: rs7224199; hg19: chr17-28523726;