rs1617769

Variant names:

• chr11-20648425-T-C
• rs1617769
• NM_004211.5:c.2070+1491T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-20648425-T-C
• chr11-20648425-T-G

Variant summary

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

The NM_004211.5(SLC6A5):​c.2070+1491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,112 control chromosomes in the GnomAD database, including 57,239 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 0.87 (57239 hom., cov: 32)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 3 publications found

Genes affected

SLC6A5 (HGNC:11051): (solute carrier family 6 member 5) This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

SLC6A5 Gene-Disease associations (from GenCC):

• hyperekplexia 3

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• hereditary hyperekplexia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004211.5. 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
	SLC6A5	NM_004211.5	MANE Select	c.2070+1491T>C		intron	N/A	NP_004202.4	Q9Y345-1
	SLC6A5	NM_001318369.2		c.1368+1491T>C		intron	N/A	NP_001305298.1	Q9Y345-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	ENST00000525748.6	TSL:1 MANE Select	c.2070+1491T>C		intron	N/A	ENSP00000434364.2	Q9Y345-1
	SLC6A5	ENST00000298923.11	TSL:1	n.*1367+1491T>C		intron	N/A	ENSP00000298923.7	J3KNC4
	SLC6A5	ENST00000528440.1	TSL:5	n.601+1491T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131685 AN: 151994 Hom.: 57184 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.866 AC: 131799 AN: 152112 Hom.: 57239 Cov.: 32 AF XY: 0.870 AC XY: 64711 AN XY: 74362

African (AFR) AF: 0.808 AC: 33482 AN: 41450

American (AMR) AF: 0.915 AC: 13993 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3204 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5148 AN: 5184

South Asian (SAS) AF: 0.848 AC: 4081 AN: 4814

European-Finnish (FIN) AF: 0.919 AC: 9753 AN: 10608

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.872 AC: 59309 AN: 67986

Other (OTH) AF: 0.873 AC: 1841 AN: 2110

Alfa AF: 0.867 Hom.: 105810

Bravo AF: 0.864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.27
PhyloP100		-2.2
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: rs1617769; hg19: chr11-20669971;