17-30211514-C-T

Position:

• chr17-30211514-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001045.6(SLC6A4):​c.1205-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 789,518 control chromosomes in the GnomAD database, including 83,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13911 hom., cov: 32)
  • Exomes 𝑓: 0.45 (69150 hom.)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.1205-90G>A		intron_variant		ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.1205-90G>A		intron_variant			NM_001045.6	ENSP00000498537	P1
SLC6A4	ENST00000261707.7	c.1205-90G>A		intron_variant		1		ENSP00000261707	P1
SLC6A4	ENST00000394821.2	c.1205-90G>A		intron_variant		1		ENSP00000378298
SLC6A4	ENST00000401766.6	c.1205-90G>A		intron_variant		5		ENSP00000385822	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62769 AN: 151934 Hom.: 13914 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.454 AC: 289591 AN: 637464 Hom.: 69150 AF XY: 0.455 AC XY: 154850 AN XY: 340354

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.806

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.413 AC: 62780 AN: 152054 Hom.: 13911 Cov.: 32 AF XY: 0.422 AC XY: 31325 AN XY: 74308

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.442

Alfa AF: 0.434 Hom.: 14624

Bravo AF: 0.420

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140701; hg19: chr17-28538532;