15-45262069-C-A

Variant names:

• chr15-45262069-C-A
• rs1060896
• NM_004212.4:c.225C>A

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.225C>A​(p.Ser75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,610,694 control chromosomes in the GnomAD database, including 308,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (20716 hom., cov: 31)
  • Exomes 𝑓: 0.61 (287307 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37
• Publications: 56 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=5.6951517E-6).
• BP6: Variant 15-45262069-C-A is Benign according to our data. Variant chr15-45262069-C-A is described in ClinVar as Benign. ClinVar VariationId is 1267759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	NM_004212.4	MANE Select	c.225C>A	p.Ser75Arg	missense	Exon 4 of 18	NP_004203.2
	SLC28A2-AS1	NR_120335.1		n.27-6071G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.225C>A	p.Ser75Arg	missense	Exon 4 of 18	ENSP00000315006.4
	SLC28A2	ENST00000560438.5	TSL:4	c.189C>A	p.Ser63Arg	missense	Exon 3 of 6	ENSP00000454074.1
	SLC28A2-AS1	ENST00000560344.6	TSL:5	n.34-6071G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71905 AN: 151958 Hom.: 20722 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.501 AC: 125660 AN: 251060 AF XY: 0.518

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.584

Gnomad EAS exome AF: 0.0855

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.653

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.611 AC: 890706 AN: 1458618 Hom.: 287307 Cov.: 34 AF XY: 0.610 AC XY: 442642 AN XY: 725744

African (AFR) AF: 0.162 AC: 5416 AN: 33416

American (AMR) AF: 0.317 AC: 14142 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 15254 AN: 26078

East Asian (EAS) AF: 0.0665 AC: 2639 AN: 39684

South Asian (SAS) AF: 0.487 AC: 41930 AN: 86078

European-Finnish (FIN) AF: 0.597 AC: 31878 AN: 53380

Middle Eastern (MID) AF: 0.523 AC: 3014 AN: 5762

European-Non Finnish (NFE) AF: 0.669 AC: 741946 AN: 1109314

Other (OTH) AF: 0.572 AC: 34487 AN: 60246

GnomAD4 genome AF: 0.473 AC: 71898 AN: 152076 Hom.: 20716 Cov.: 31 AF XY: 0.464 AC XY: 34527 AN XY: 74344

African (AFR) AF: 0.182 AC: 7541 AN: 41476

American (AMR) AF: 0.408 AC: 6230 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2014 AN: 3468

East Asian (EAS) AF: 0.0956 AC: 495 AN: 5178

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4816

European-Finnish (FIN) AF: 0.601 AC: 6348 AN: 10556

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45238 AN: 67986

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.559 Hom.: 48463

Bravo AF: 0.443

TwinsUK AF: 0.672 AC: 2493

ALSPAC AF: 0.663 AC: 2555

ESP6500AA AF: 0.196 AC: 861

ESP6500EA AF: 0.665 AC: 5714

ExAC AF: 0.502 AC: 60912

Asia WGS AF: 0.279 AC: 971 AN: 3478

EpiCase AF: 0.654

EpiControl AF: 0.651

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	0.097
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.21
DANN	Benign	0.87
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0000057	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.26	N
PhyloP100		-1.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.28	N
REVEL	Uncertain	0.35
Sift	Benign	0.56	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.16		Gain of MoRF binding (P = 0.0107)
MPC		0.044
ClinPred		0.0013	T
GERP RS		-3.7
Varity_R		0.052
gMVP		0.13
Mutation Taster		=99/1	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: rs1060896; hg19: chr15-45554267; COSMIC: COSV61665205; COSMIC: COSV61665205;