rs2453580

Variant names:

• chr17-19535008-T-C
• rs2453580
• NM_018242.3:c.135+934T>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.135+934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,154 control chromosomes in the GnomAD database, including 10,740 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 0.37 (10716 hom., cov: 32)
  • Exomes 𝑓: 0.47 (24 hom.)
• Consequence: SLC47A1 NM_018242.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 32 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	NM_018242.3	MANE Select	c.135+934T>C		intron	N/A	NP_060712.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.135+934T>C		intron	N/A	ENSP00000270570.4	Q96FL8-1
	SLC47A1	ENST00000395585.5	TSL:1	c.135+934T>C		intron	N/A	ENSP00000378951.1	Q96FL8-3
	SLC47A1	ENST00000571335.5	TSL:1	c.-311+1437T>C		intron	N/A	ENSP00000462630.1	J3KSS8

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55640 AN: 151850 Hom.: 10720 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.468 AC: 87 AN: 186 Hom.: 24 Cov.: 0 AF XY: 0.458 AC XY: 65 AN XY: 142

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.333 AC: 2 AN: 6

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.476 AC: 79 AN: 166

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.366 AC: 55670 AN: 151968 Hom.: 10716 Cov.: 32 AF XY: 0.355 AC XY: 26381 AN XY: 74274

African (AFR) AF: 0.393 AC: 16283 AN: 41452

American (AMR) AF: 0.305 AC: 4648 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1543 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1100 AN: 5146

South Asian (SAS) AF: 0.192 AC: 925 AN: 4820

European-Finnish (FIN) AF: 0.271 AC: 2858 AN: 10552

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27024 AN: 67952

Other (OTH) AF: 0.392 AC: 824 AN: 2104

Alfa AF: 0.393 Hom.: 41759

Bravo AF: 0.373

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		0.58
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: rs2453580; hg19: chr17-19438321;