rs3781742

Variant names:

• chr11-20609400-G-A
• rs3781742
• NM_004211.5:c.985+1748G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-20609400-G-A
• chr11-20609400-G-C
• chr11-20609400-G-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.985+1748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 151,754 control chromosomes in the GnomAD database, including 626 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 0.056 (626 hom., cov: 32)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.985+1748G>A		intron_variant	Intron 5 of 15	ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.283+1748G>A		intron_variant	Intron 4 of 14		NP_001305298.1
SLC6A5	XM_017018544.3	c.109+2262G>A		intron_variant	Intron 1 of 11		XP_016874033.1
SLC6A5	XR_007062528.1	n.363+1748G>A		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.985+1748G>A		intron_variant	Intron 5 of 15	1	NM_004211.5	ENSP00000434364.2
SLC6A5	ENST00000298923.11	n.*282+1748G>A		intron_variant	Intron 4 of 14	1		ENSP00000298923.7

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8406 AN: 151638 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0955

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0514

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

GnomAD4 genome AF: 0.0555 AC: 8428 AN: 151754 Hom.: 626 Cov.: 32 AF XY: 0.0587 AC XY: 4349 AN XY: 74138

African (AFR) AF: 0.0125 AC: 517 AN: 41328

American (AMR) AF: 0.127 AC: 1933 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 331 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1809 AN: 5116

South Asian (SAS) AF: 0.0387 AC: 186 AN: 4804

European-Finnish (FIN) AF: 0.0785 AC: 824 AN: 10502

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2715 AN: 67978

Other (OTH) AF: 0.0509 AC: 107 AN: 2102

Alfa AF: 0.0177 Hom.: 11

Bravo AF: 0.0633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		-0.22
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: rs3781742; hg19: chr11-20630946;