rs2247436

Variant names:

• chr17-19551420-G-A
• rs2247436
• NM_018242.3:c.499-4G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_018242.3(SLC47A1):​c.499-4G>A variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00001470
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018242.3. 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
	SLC47A1	NM_018242.3	MANE Select	c.499-4G>A		splice_region intron	N/A	NP_060712.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.499-4G>A		splice_region intron	N/A	ENSP00000270570.4
	SLC47A1	ENST00000395585.5	TSL:1	c.499-4G>A		splice_region intron	N/A	ENSP00000378951.1
	SLC47A1	ENST00000571335.5	TSL:1	c.54-4G>A		splice_region intron	N/A	ENSP00000462630.1

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

GnomAD2 exomes AF: 0.200 AC: 50300 AN: 251178 AF XY: 0.198

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 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

African (AFR) AF: 0.142 AC: 4675 AN: 32914

American (AMR) AF: 0.204 AC: 9106 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3287 AN: 25988

East Asian (EAS) AF: 0.438 AC: 17242 AN: 39404

South Asian (SAS) AF: 0.181 AC: 15475 AN: 85568

European-Finnish (FIN) AF: 0.206 AC: 11001 AN: 53290

Middle Eastern (MID) AF: 0.122 AC: 698 AN: 5724

European-Non Finnish (NFE) AF: 0.180 AC: 194483 AN: 1080750

Other (OTH) AF: 0.185 AC: 10966 AN: 59268

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

African (AFR) AF: 0.144 AC: 5983 AN: 41500

American (AMR) AF: 0.188 AC: 2867 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2048 AN: 5146

South Asian (SAS) AF: 0.183 AC: 881 AN: 4820

European-Finnish (FIN) AF: 0.208 AC: 2194 AN: 10556

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12533 AN: 67950

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.185 Hom.: 2502

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.80
DANN	Benign	0.59
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2247436; hg19: chr17-19454733; COSMIC: COSV54500636; COSMIC: COSV54500636;