rs34012597

Variant names:

• chr17-19546467-C-T
• rs34012597
• ENST00000571335.5:c.-176C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000571335.5(SLC47A1):​c.-176C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,613,738 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (49 hom.)
• Consequence: SLC47A1 ENST00000571335.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-19546467-C-T is Benign according to our data. Variant chr17-19546467-C-T is described in ClinVar as Benign. ClinVar VariationId is 784668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000571335.5. 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.270C>T	p.Phe90Phe	synonymous	Exon 3 of 17	NP_060712.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC47A1	ENST00000571335.5	TSL:1	c.-176C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	ENSP00000462630.1	J3KSS8
	SLC47A1	ENST00000270570.8	TSL:1 MANE Select	c.270C>T	p.Phe90Phe	synonymous	Exon 3 of 17	ENSP00000270570.4	Q96FL8-1
	SLC47A1	ENST00000395585.5	TSL:1	c.270C>T	p.Phe90Phe	synonymous	Exon 3 of 19	ENSP00000378951.1	Q96FL8-3

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2354 AN: 151858 Hom.: 61 Cov.: 31

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00848

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00447 AC: 1123 AN: 251202 AF XY: 0.00348

Gnomad AFR exome AF: 0.0549

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000651

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00195 AC: 2847 AN: 1461762 Hom.: 49 Cov.: 31 AF XY: 0.00177 AC XY: 1286 AN XY: 727156

African (AFR) AF: 0.0542 AC: 1815 AN: 33470

American (AMR) AF: 0.00403 AC: 180 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000482 AC: 536 AN: 1111970

Other (OTH) AF: 0.00409 AC: 247 AN: 60392

GnomAD4 genome AF: 0.0155 AC: 2356 AN: 151976 Hom.: 61 Cov.: 31 AF XY: 0.0151 AC XY: 1123 AN XY: 74292

African (AFR) AF: 0.0524 AC: 2172 AN: 41426

American (AMR) AF: 0.00847 AC: 129 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68002

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00916 Hom.: 13

Bravo AF: 0.0179

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000889

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.0
DANN	Benign	0.46
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34012597; hg19: chr17-19449780;