rs2020935

Variant names:

• chr17-30234437-T-A
• rs2020935
• NM_001045.6:c.-221+1176A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001045.6(SLC6A4):​c.-221+1176A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,170 control chromosomes in the GnomAD database, including 1,172 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 0.10 (1172 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-221+1176A>T		intron_variant	Intron 1 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.-221+1176A>T		intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-221+1176A>T		intron_variant	Intron 1 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-221+1176A>T		intron_variant	Intron 1 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-124+1176A>T		intron_variant	Intron 1 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15162 AN: 152052 Hom.: 1169 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0999 AC: 15200 AN: 152170 Hom.: 1172 Cov.: 32 AF XY: 0.0965 AC XY: 7188 AN XY: 74452

African (AFR) AF: 0.212 AC: 8804 AN: 41484

American (AMR) AF: 0.0636 AC: 972 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5178

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4824

European-Finnish (FIN) AF: 0.0282 AC: 299 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0636 AC: 4324 AN: 67992

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0892 Hom.: 109

Bravo AF: 0.107

Asia WGS AF: 0.0360 AC: 127 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	2.0
DANN	Benign	0.52
PhyloP100		-0.51
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: rs2020935; hg19: chr17-28561455;