19-46784682-T-C

Variant names:

• chr19-46784682-T-C
• rs313853
• NM_005628.3:c.567-123A>G

Variant summary

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

The NM_005628.3(SLC1A5):​c.567-123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,595,402 control chromosomes in the GnomAD database, including 91,900 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 0.33 (8586 hom., cov: 32)
  • Exomes 𝑓: 0.34 (83314 hom.)
• Consequence: SLC1A5 NM_005628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005628.3. 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
	SLC1A5	NM_005628.3	MANE Select	c.567-123A>G		intron	N/A	NP_005619.1
	SLC1A5	NM_001145145.2		c.-85A>G		5_prime_UTR	Exon 1 of 7	NP_001138617.1
	SLC1A5	NM_001145144.2		c.-118-123A>G		intron	N/A	NP_001138616.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A5	ENST00000542575.6	TSL:1 MANE Select	c.567-123A>G		intron	N/A	ENSP00000444408.1
	SLC1A5	ENST00000594991.5	TSL:2	c.-85A>G		5_prime_UTR	Exon 1 of 7	ENSP00000469265.1
	SLC1A5	ENST00000434726.6	TSL:2	c.-85A>G		5_prime_UTR	Exon 1 of 7	ENSP00000406532.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50718 AN: 151872 Hom.: 8580 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.333 AC: 72403 AN: 217328 AF XY: 0.336

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.380

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.339 AC: 489243 AN: 1443412 Hom.: 83314 Cov.: 34 AF XY: 0.339 AC XY: 243221 AN XY: 716752

African (AFR) AF: 0.336 AC: 11152 AN: 33146

American (AMR) AF: 0.283 AC: 11784 AN: 41654

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8539 AN: 25084

East Asian (EAS) AF: 0.266 AC: 10428 AN: 39258

South Asian (SAS) AF: 0.341 AC: 28767 AN: 84438

European-Finnish (FIN) AF: 0.382 AC: 19898 AN: 52132

Middle Eastern (MID) AF: 0.291 AC: 1630 AN: 5596

European-Non Finnish (NFE) AF: 0.343 AC: 377815 AN: 1102400

Other (OTH) AF: 0.322 AC: 19230 AN: 59704

GnomAD4 genome AF: 0.334 AC: 50744 AN: 151990 Hom.: 8586 Cov.: 32 AF XY: 0.331 AC XY: 24576 AN XY: 74262

African (AFR) AF: 0.340 AC: 14085 AN: 41464

American (AMR) AF: 0.272 AC: 4152 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1311 AN: 5160

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4824

European-Finnish (FIN) AF: 0.385 AC: 4060 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23347 AN: 67950

Other (OTH) AF: 0.301 AC: 636 AN: 2110

Alfa AF: 0.338 Hom.: 24288

Bravo AF: 0.325

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-1.8
PromoterAI		0.055	Neutral
Mutation Taster		=300/0	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: rs313853; hg19: chr19-47287939; COSMIC: COSV69466742; COSMIC: COSV69466742;