Genetic Variant NM_004213.5:c.124T>C (chr15-84888799-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_004213.5(SLC28A1):c.124T>C(p.Leu42Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,554,436 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0093 ( 12 hom., cov: 32)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

SLC28A1
NM_004213.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.988

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:

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=-0.91).

BP6

Variant 15-84888799-T-C is Benign according to our data. Variant chr15-84888799-T-C is described in ClinVar as [Benign]. Clinvar id is 3042333.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0114 (15971/1402188) while in subpopulation EAS AF= 0.0182 (655/35984). AF 95% confidence interval is 0.017. There are 120 homozygotes in gnomad4_exome. There are 7554 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.124T>C	p.Leu42Leu	synonymous_variant	Exon 4 of 19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.124T>C	p.Leu42Leu	synonymous_variant	Exon 4 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.124T>C	p.Leu42Leu	synonymous_variant	Exon 3 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.124T>C	p.Leu42Leu	synonymous_variant	Exon 4 of 7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.124T>C	p.Leu42Leu	synonymous_variant	Exon 3 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.00929

AC:

1413

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.00909

AC:

1440

AN:

158484

Hom.:

AF XY:

0.00830

AC XY:

696

AN XY:

83892

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.00984

Gnomad ASJ exome

AF:

0.00983

Gnomad EAS exome

AF:

0.00995

Gnomad SAS exome

AF:

0.00244

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0114

AC:

15971

AN:

1402188

Hom.:

120

Cov.:

AF XY:

0.0109

AC XY:

7554

AN XY:

692014

show subpopulations

Gnomad4 AFR exome

AF:

0.00545

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0182

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.00929

AC:

1415

AN:

152248

Hom.:

Cov.:

AF XY:

0.00844

AC XY:

628

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00549

Gnomad4 AMR

AF:

0.0127

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Nov 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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

-0.91

CADD

Benign

0.19

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over