Genetic Variant SLC28A1:c.-16-7C>T (chr15-84887738-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004213.5(SLC28A1):c.-16-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,611,914 control chromosomes in the GnomAD database, including 35,921 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2727 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33194 hom. )

Consequence

SLC28A1
NM_004213.5 splice_region, intron

Scores

Splicing: ADA: 0.00001670

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.523

Variant links:

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]

SLC28A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.-16-7C>T		splice_region_variant, intron_variant	Intron 2 of 18	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.-16-7C>T	splice_region_variant, intron_variant	Intron 2 of 18	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.-16-7C>T	splice_region_variant, intron_variant	Intron 1 of 17	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.-16-7C>T	splice_region_variant, intron_variant	Intron 2 of 6	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.-16-7C>T	splice_region_variant, intron_variant	Intron 1 of 14	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25384

AN:

152060

Hom.:

2732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0397

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.192

AC:

48161

AN:

251242

Hom.:

5099

AF XY:

0.193

AC XY:

26269

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.209

AC:

304862

AN:

1459736

Hom.:

33194

Cov.:

AF XY:

0.209

AC XY:

151521

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.167

AC:

25367

AN:

152178

Hom.:

2727

Cov.:

AF XY:

0.167

AC XY:

12398

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.214

Hom.:

7128

Bravo

AF:

0.159

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over