rs2070246

Positions:

• chr19-46778905-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005628.3(SLC1A5):​c.828C>T​(p.Tyr276Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,557,940 control chromosomes in the GnomAD database, including 45,213 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 0.29 (7320 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37893 hom.)
• Consequence: SLC1A5 NM_005628.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

Genes affected

SLC1A5 (HGNC:10943): (solute carrier family 1 member 5) The SLC1A5 gene encodes a sodium-dependent neutral amino acid transporter that can act as a receptor for RD114/type D retrovirus (Larriba et al., 2001 [PubMed 11781704]).[supplied by OMIM, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.546 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A5	NM_005628.3	c.828C>T	p.Tyr276Tyr	synonymous_variant	5/8	ENST00000542575.6	NP_005619.1
SLC1A5	NM_001145145.2	c.222C>T	p.Tyr74Tyr	synonymous_variant	4/7		NP_001138617.1
SLC1A5	NM_001145144.2	c.144C>T	p.Tyr48Tyr	synonymous_variant	5/8		NP_001138616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A5	ENST00000542575.6	c.828C>T	p.Tyr276Tyr	synonymous_variant	5/8	1	NM_005628.3	ENSP00000444408.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44086 AN: 152046 Hom.: 7303 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.271 AC: 55351 AN: 203922 Hom.: 8363 AF XY: 0.261 AC XY: 28129 AN XY: 107708

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.259

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.224 AC: 314753 AN: 1405774 Hom.: 37893 Cov.: 33 AF XY: 0.225 AC XY: 155822 AN XY: 693240

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.290 AC: 44153 AN: 152166 Hom.: 7320 Cov.: 32 AF XY: 0.293 AC XY: 21776 AN XY: 74386

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.280

Alfa AF: 0.242 Hom.: 4765

Bravo AF: 0.311

Asia WGS AF: 0.311 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.7
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2070246; hg19: chr19-47282162; COSMIC: COSV69466977; COSMIC: COSV69466977;