15-45253280-C-T

Variant names:

• chr15-45253280-C-T
• rs11854484
• NM_004212.4:c.65C>T

Variant summary

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

The NM_004212.4(SLC28A2):​c.65C>T​(p.Pro22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,236 control chromosomes in the GnomAD database, including 279,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (18965 hom., cov: 32)
  • Exomes 𝑓: 0.58 (260927 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79
• Publications: 52 publications found

Genes affected

SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.6209626E-6).
• BP6: Variant 15-45253280-C-T is Benign according to our data. Variant chr15-45253280-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004212.4. 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
	SLC28A2	NM_004212.4	MANE Select	c.65C>T	p.Pro22Leu	missense	Exon 2 of 18	NP_004203.2
	SLC28A2-AS1	NR_120335.1		n.180+586G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.65C>T	p.Pro22Leu	missense	Exon 2 of 18	ENSP00000315006.4
	SLC28A2	ENST00000959719.1		c.65C>T	p.Pro22Leu	missense	Exon 2 of 18	ENSP00000629778.1
	SLC28A2	ENST00000959720.1		c.65C>T	p.Pro22Leu	missense	Exon 2 of 17	ENSP00000629779.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68700 AN: 151942 Hom.: 18972 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.474 AC: 118542 AN: 250026 AF XY: 0.491

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.0793

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.582 AC: 848558 AN: 1458176 Hom.: 260927 Cov.: 33 AF XY: 0.581 AC XY: 421374 AN XY: 725480

African (AFR) AF: 0.157 AC: 5235 AN: 33450

American (AMR) AF: 0.299 AC: 13324 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13369 AN: 26104

East Asian (EAS) AF: 0.0627 AC: 2490 AN: 39686

South Asian (SAS) AF: 0.464 AC: 39886 AN: 86042

European-Finnish (FIN) AF: 0.588 AC: 31370 AN: 53364

Middle Eastern (MID) AF: 0.467 AC: 2693 AN: 5762

European-Non Finnish (NFE) AF: 0.638 AC: 707458 AN: 1108844

Other (OTH) AF: 0.543 AC: 32733 AN: 60302

GnomAD4 genome AF: 0.452 AC: 68704 AN: 152060 Hom.: 18965 Cov.: 32 AF XY: 0.445 AC XY: 33086 AN XY: 74322

African (AFR) AF: 0.177 AC: 7326 AN: 41478

American (AMR) AF: 0.387 AC: 5915 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.0874 AC: 452 AN: 5174

South Asian (SAS) AF: 0.431 AC: 2077 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6261 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43157 AN: 67974

Other (OTH) AF: 0.463 AC: 979 AN: 2114

Alfa AF: 0.553 Hom.: 92380

Bravo AF: 0.421

TwinsUK AF: 0.644 AC: 2387

ALSPAC AF: 0.631 AC: 2433

ESP6500AA AF: 0.191 AC: 840

ESP6500EA AF: 0.628 AC: 5402

ExAC AF: 0.474 AC: 57598

Asia WGS AF: 0.265 AC: 922 AN: 3478

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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.71
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.056
Sift	Benign	0.55	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.042
MPC		0.042
ClinPred		0.0066	T
GERP RS		-0.81
Varity_R		0.023
gMVP		0.16
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11854484; hg19: chr15-45545478; COSMIC: COSV61664096; COSMIC: COSV61664096;