chr15-84888762-C-T

Variant names:

• chr15-84888762-C-T
• rs8187742
• NM_004213.5:c.97-10C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_004213.5(SLC28A1):​c.97-10C>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.00004090
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.254

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.97-10C>T		intron_variant	Intron 3 of 18	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.97-10C>T		intron_variant	Intron 3 of 18	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.97-10C>T		intron_variant	Intron 2 of 17	1		ENSP00000286749.3
SLC28A1	ENST00000338602.6	c.97-10C>T		intron_variant	Intron 3 of 6	1		ENSP00000341629.2
SLC28A1	ENST00000538177.5	c.97-10C>T		intron_variant	Intron 2 of 14	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes AF: 0.00503 AC: 766 AN: 152196 Hom.: 5 Cov.: 32

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

GnomAD2 exomes AF: 0.00136 AC: 210 AN: 154606 AF XY: 0.000953

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 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

Gnomad4 AFR exome AF: 0.0172 AC: 544 AN: 31612

Gnomad4 AMR exome AF: 0.00131 AC: 47 AN: 35796

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25172

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35784

Gnomad4 SAS exome AF: 0.0000252 AC: 2 AN: 79218

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49076

Gnomad4 NFE exome AF: 0.0000965 AC: 104 AN: 1077194

Gnomad4 Remaining exome AF: 0.00135 AC: 78 AN: 57884

GnomAD4 genome AF: 0.00506 AC: 770 AN: 152314 Hom.: 5 Cov.: 32 AF XY: 0.00485 AC XY: 361 AN XY: 74472

Gnomad4 AFR AF: 0.0173 AC: 0.0173011 AN: 0.0173011

Gnomad4 AMR AF: 0.00183 AC: 0.00182935 AN: 0.00182935

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000193 AC: 0.000192827 AN: 0.000192827

Gnomad4 SAS AF: 0.000207 AC: 0.000207039 AN: 0.000207039

Gnomad4 FIN AF: 0.0000941 AC: 0.0000941442 AN: 0.0000941442

Gnomad4 NFE AF: 0.000221 AC: 0.000220523 AN: 0.000220523

Gnomad4 OTH AF: 0.00237 AC: 0.00236518 AN: 0.00236518

Alfa AF: 0.00204 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

Submissions by phenotype

SLC28A1-related disorder Benign:1

Dec 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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