rs2252281

Variant names:

• chr17-19533874-T-C
• rs2252281
• NM_018242.3:c.-66T>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.-66T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,378,710 control chromosomes in the GnomAD database, including 74,717 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 0.32 (7606 hom., cov: 32)
  • Exomes 𝑓: 0.32 (67111 hom.)
• Consequence: SLC47A1 NM_018242.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 53 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A1	NM_018242.3	c.-66T>C		5_prime_UTR_variant	Exon 1 of 17	ENST00000270570.8	NP_060712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8	c.-66T>C		5_prime_UTR_variant	Exon 1 of 17	1	NM_018242.3	ENSP00000270570.4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 46651 AN: 146856 Hom.: 7605 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.324 AC: 398702 AN: 1231760 Hom.: 67111 Cov.: 30 AF XY: 0.321 AC XY: 191879 AN XY: 598562

African (AFR) AF: 0.379 AC: 8657 AN: 22814

American (AMR) AF: 0.194 AC: 3515 AN: 18134

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 6981 AN: 18308

East Asian (EAS) AF: 0.180 AC: 5241 AN: 29110

South Asian (SAS) AF: 0.185 AC: 11067 AN: 59692

European-Finnish (FIN) AF: 0.234 AC: 7127 AN: 30458

Middle Eastern (MID) AF: 0.329 AC: 1139 AN: 3464

European-Non Finnish (NFE) AF: 0.339 AC: 339009 AN: 998972

Other (OTH) AF: 0.314 AC: 15966 AN: 50808

GnomAD4 genome AF: 0.318 AC: 46677 AN: 146950 Hom.: 7606 Cov.: 32 AF XY: 0.308 AC XY: 22137 AN XY: 71930

African (AFR) AF: 0.375 AC: 14246 AN: 38038

American (AMR) AF: 0.252 AC: 3776 AN: 14998

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1374 AN: 3452

East Asian (EAS) AF: 0.215 AC: 1073 AN: 4988

South Asian (SAS) AF: 0.172 AC: 812 AN: 4730

European-Finnish (FIN) AF: 0.225 AC: 2354 AN: 10474

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.328 AC: 22002 AN: 67020

Other (OTH) AF: 0.331 AC: 682 AN: 2058

Alfa AF: 0.385 Hom.: 1036

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		0.0
PromoterAI		-0.14	Neutral
Mutation Taster		=299/1	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: rs2252281; hg19: chr17-19437187;