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. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.1870-248G>A		intron_variant	Intron 12 of 15	ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.1168-248G>A		intron_variant	Intron 11 of 14		NP_001305298.1
SLC6A5	XM_017018544.3	c.994-248G>A		intron_variant	Intron 8 of 11		XP_016874033.1
SLC6A5	XR_007062528.1	n.1248-248G>A		intron_variant	Intron 9 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.1870-248G>A		intron_variant	Intron 12 of 15	1	NM_004211.5	ENSP00000434364.2
SLC6A5	ENST00000298923.11	n.*1167-248G>A		intron_variant	Intron 11 of 14	1		ENSP00000298923.7
SLC6A5	ENST00000528440.1	n.401-248G>A		intron_variant	Intron 4 of 7	5

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

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.333

Alfa AF: 0.310 Hom.: 1911

Bravo AF: 0.349

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298826; hg19: chr11-20659757;