rs2247436

Positions:

• chr17-19551420-G-A
• chr17-19551420-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018242.3(SLC47A1):​c.499-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,579,582 control chromosomes in the GnomAD database, including 30,570 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2623 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27947 hom.)
• Consequence: SLC47A1 NM_018242.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001470
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

SLC47A1 (HGNC:25588): (solute carrier family 47 member 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It encodes a protein of unknown function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC47A1	NM_018242.3	c.499-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000270570.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC47A1	ENST00000270570.8	c.499-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018242.3	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27453 AN: 151912 Hom.: 2623 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.200 AC: 50300 AN: 251178 Hom.: 5434 AF XY: 0.198 AC XY: 26903 AN XY: 135788

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.393

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.187 AC: 266933 AN: 1427552 Hom.: 27947 Cov.: 30 AF XY: 0.187 AC XY: 133229 AN XY: 711596

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.181 AC: 27486 AN: 152030 Hom.: 2623 Cov.: 32 AF XY: 0.183 AC XY: 13605 AN XY: 74320

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.176

Alfa AF: 0.181 Hom.: 1716

Bravo AF: 0.178

Asia WGS AF: 0.264 AC: 920 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.80
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.080		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: rs2247436; hg19: chr17-19454733; COSMIC: COSV54500636; COSMIC: COSV54500636;