rs1945771

Variant names:

• chr11-20632075-C-A
• rs1945771
• NM_004211.5:c.1624+1260C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-20632075-C-A
• chr11-20632075-C-T

Variant summary

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

The NM_004211.5(SLC6A5):​c.1624+1260C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,000 control chromosomes in the GnomAD database, including 7,891 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 0.31 (7891 hom., cov: 32)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• 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 Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	NM_004211.5	MANE Select	c.1624+1260C>A		intron	N/A	NP_004202.4
	SLC6A5	NM_001318369.2		c.922+1260C>A		intron	N/A	NP_001305298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	ENST00000525748.6	TSL:1 MANE Select	c.1624+1260C>A		intron	N/A	ENSP00000434364.2
	SLC6A5	ENST00000298923.11	TSL:1	n.*921+1260C>A		intron	N/A	ENSP00000298923.7
	SLC6A5	ENST00000528440.1	TSL:5	n.155+1260C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47315 AN: 151882 Hom.: 7889 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.311 AC: 47322 AN: 152000 Hom.: 7891 Cov.: 32 AF XY: 0.310 AC XY: 23019 AN XY: 74296

African (AFR) AF: 0.188 AC: 7794 AN: 41480

American (AMR) AF: 0.333 AC: 5082 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1483 AN: 5146

South Asian (SAS) AF: 0.253 AC: 1213 AN: 4798

European-Finnish (FIN) AF: 0.346 AC: 3661 AN: 10568

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25470 AN: 67954

Other (OTH) AF: 0.342 AC: 720 AN: 2106

Alfa AF: 0.218 Hom.: 549

Bravo AF: 0.304

Asia WGS AF: 0.267 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.69
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: rs1945771; hg19: chr11-20653621;