15-84888762-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004213.5(SLC28A1):​c.97-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,549,480 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 6 hom. )

Consequence

SLC28A1
NM_004213.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00004090
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.254
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 15-84888762-C-T is Benign according to our data. Variant chr15-84888762-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056473.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00506 (770/152314) while in subpopulation AFR AF= 0.0173 (719/41558). AF 95% confidence interval is 0.0163. There are 5 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC28A1NM_004213.5 linkuse as main transcriptc.97-10C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000394573.6 NP_004204.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC28A1ENST00000394573.6 linkuse as main transcriptc.97-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_004213.5 ENSP00000378074 P1O00337-1
SLC28A1ENST00000286749.3 linkuse as main transcriptc.97-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000286749 P1O00337-1
SLC28A1ENST00000338602.6 linkuse as main transcriptc.97-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000341629 O00337-2
SLC28A1ENST00000538177.5 linkuse as main transcriptc.97-10C>T splice_polypyrimidine_tract_variant, intron_variant 2 ENSP00000443752

Frequencies

GnomAD3 genomes
AF:
0.00503
AC:
766
AN:
152196
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0173
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00136
AC:
210
AN:
154606
Hom.:
2
AF XY:
0.000953
AC XY:
78
AN XY:
81874
show subpopulations
Gnomad AFR exome
AF:
0.0192
Gnomad AMR exome
AF:
0.00117
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000176
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000154
Gnomad OTH exome
AF:
0.000905
GnomAD4 exome
AF:
0.000560
AC:
783
AN:
1397166
Hom.:
6
Cov.:
30
AF XY:
0.000453
AC XY:
312
AN XY:
689408
show subpopulations
Gnomad4 AFR exome
AF:
0.0172
Gnomad4 AMR exome
AF:
0.00131
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000252
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000965
Gnomad4 OTH exome
AF:
0.00135
GnomAD4 genome
AF:
0.00506
AC:
770
AN:
152314
Hom.:
5
Cov.:
32
AF XY:
0.00485
AC XY:
361
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0173
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00125
Hom.:
1
Bravo
AF:
0.00578
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SLC28A1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 26, 2019This variant is classified as likely 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
BayesDel_noAF
Benign
-0.90
CADD
Benign
4.9
DANN
Benign
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000041
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.

Other links and lift over

dbSNP: rs8187742; hg19: chr15-85431993; COSMIC: COSV99723541; API