rs1051266

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1

The NM_194255.4(SLC19A1):c.80A>G(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,600,100 control chromosomes in the GnomAD database, including 249,464 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

Frequency

Genomes: 𝑓 0.52 ( 20951 hom., cov: 32)

Exomes 𝑓: 0.56 ( 228513 hom. )

Consequence

SLC19A1
NM_194255.4 missense

Scores

Clinical Significance

drug response reviewed by expert panel P:1U:1B:1O:1

Conservation

PhyloP100: 0.987

Variant links:

Genes affected

SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

SLC19A1 links:

SLC19A1 (HGNC:):

SLC19A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8591234E-5).

BP6

Variant 21-45537880-T-C is Benign according to our data. Variant chr21-45537880-T-C is described in ClinVar as [drug_response]. Clinvar id is 157588.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=1, drug_response=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4 linkuse as main transcript	c.80A>G	p.His27Arg	missense_variant	2/6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9 linkuse as main transcript	c.80A>G	p.His27Arg	missense_variant	2/6	1	NM_194255.4	ENSP00000308895.4		P41440-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78652

AN:

151888

Hom.:

20924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.503

GnomAD3 exomes

AF:

0.550

AC:

125992

AN:

228958

Hom.:

34859

AF XY:

0.556

AC XY:

69279

AN XY:

124500

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.601

Gnomad EAS exome

AF:

0.471

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.541

GnomAD4 exome

AF:

0.560

AC:

811122

AN:

1448094

Hom.:

228513

Cov.:

AF XY:

0.562

AC XY:

404045

AN XY:

719546

show subpopulations

Gnomad4 AFR exome

AF:

0.373

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.595

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.590

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.518

AC:

78718

AN:

152006

Hom.:

20951

Cov.:

AF XY:

0.519

AC XY:

38536

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.594

Gnomad4 FIN

AF:

0.548

Gnomad4 NFE

AF:

0.572

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.561

Hom.:

43663

Bravo

AF:

0.512

TwinsUK

AF:

0.559

AC:

2073

ALSPAC

AF:

0.573

AC:

2208

ESP6500AA

AF:

0.391

AC:

1717

ESP6500EA

AF:

0.569

AC:

4894

ExAC

AF:

0.533

AC:

64099

Asia WGS

AF:

0.534

AC:

1854

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Pathogenic:1Uncertain:1Benign:1Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Lung cancer

Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Scientific Research Center, Shenzhen Evergreen Medical Institute

- -

Gastrointestinal stromal tumor

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Department of Pharmacy and Biotechnology, University of Bologna

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

methotrexate response - Efficacy

Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

6.1

DANN

Benign

0.50

DEOGEN2

Benign

0.13

T;T;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.12

T;T;T;T;T;T

MetaRNN

Benign

0.000019

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

.;N;N;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.61

N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.35

T;T;T;T;T;T

Sift4G

Benign

0.35

T;T;T;.;.;.

Polyphen

0.0

.;B;.;.;.;.

Vest4

0.0080

MPC

0.11

ClinPred

0.0042

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.021

gMVP

0.34

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