rs2298826

Variant names:

• chr11-20638211-G-A
• rs2298826
• NM_004211.5:c.1870-248G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-20638211-G-A
• chr11-20638211-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004211.5(SLC6A5):​c.1870-248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,034 control chromosomes in the GnomAD database, including 9,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9162 hom., cov: 32)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.445
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-20638211-G-A is Benign according to our data. Variant chr11-20638211-G-A is described in ClinVar as Benign. ClinVar VariationId is 1228866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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.1870-248G>A		intron	N/A	NP_004202.4
	SLC6A5	NM_001318369.2		c.1168-248G>A		intron	N/A	NP_001305298.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	ENST00000525748.6	TSL:1 MANE Select	c.1870-248G>A		intron	N/A	ENSP00000434364.2
	SLC6A5	ENST00000298923.11	TSL:1	n.*1167-248G>A		intron	N/A	ENSP00000298923.7
	SLC6A5	ENST00000528440.1	TSL:5	n.401-248G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52149 AN: 151916 Hom.: 9153 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.343 AC: 52177 AN: 152034 Hom.: 9162 Cov.: 32 AF XY: 0.339 AC XY: 25166 AN XY: 74300

African (AFR) AF: 0.320 AC: 13258 AN: 41484

American (AMR) AF: 0.301 AC: 4601 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2792 AN: 5174

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3235 AN: 10546

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24837 AN: 67958

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.331 Hom.: 4299

Bravo AF: 0.349

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.77
PhyloP100		-0.45
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: rs2298826; hg19: chr11-20659757;