rs2242046

Positions:

• chr15-84935498-G-A
• chr15-84935498-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004213.5(SLC28A1):​c.1561G>A​(p.Asp521Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,130 control chromosomes in the GnomAD database, including 169,648 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (11846 hom., cov: 33)
  • Exomes 𝑓: 0.45 (157802 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.02

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5131863E-5).
• BP6: Variant 15-84935498-G-A is Benign according to our data. Variant chr15-84935498-G-A is described in ClinVar as [Benign]. Clinvar id is 3059229.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.1561G>A	p.Asp521Asn	missense_variant	15/19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.1561G>A	p.Asp521Asn	missense_variant	15/19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.1561G>A	p.Asp521Asn	missense_variant	14/18	1		ENSP00000286749.3
SLC28A1	ENST00000538177.5	c.1084-7947G>A		intron_variant		2		ENSP00000443752.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52685 AN: 152016 Hom.: 11854 Cov.: 33

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.388

GnomAD3 exomes AF: 0.374 AC: 93823 AN: 250790 Hom.: 21090 AF XY: 0.387 AC XY: 52540 AN XY: 135618

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.0750

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.450 AC: 657428 AN: 1460996 Hom.: 157802 Cov.: 43 AF XY: 0.449 AC XY: 326253 AN XY: 726818

Gnomad4 AFR exome AF: 0.0854

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.0673

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.346 AC: 52660 AN: 152134 Hom.: 11846 Cov.: 33 AF XY: 0.340 AC XY: 25324 AN XY: 74376

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.383

Alfa AF: 0.478 Hom.: 44676

Bravo AF: 0.323

TwinsUK AF: 0.489 AC: 1814

ALSPAC AF: 0.479 AC: 1846

ESP6500AA AF: 0.103 AC: 456

ESP6500EA AF: 0.498 AC: 4278

ExAC AF: 0.375 AC: 45541

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC28A1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.96
DEOGEN2	Benign	0.0069	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.18	T;.
MetaRNN	Benign	0.000035	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.45	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.0080
Sift	Benign	0.13	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.025	B;B
Vest4		0.030
MPC		0.075
ClinPred		0.017	T
GERP RS		-0.14
Varity_R		0.041
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2242046; hg19: chr15-85478729; COSMIC: COSV54478445; COSMIC: COSV54478445;