Variant 21-45516028-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_194255.4(SLC19A1):c.1406C>T(p.Ala469Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,578,286 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 24 hom., cov: 34)

Exomes 𝑓: 0.0021 ( 39 hom. )

Consequence

SLC19A1
NM_194255.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.144

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028970242).

BP6

Variant 21-45516028-G-A is Benign according to our data. Variant chr21-45516028-G-A is described in ClinVar as [Benign]. Clinvar id is 1652889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45516028-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1619/152320) while in subpopulation AFR AF= 0.0336 (1396/41568). AF 95% confidence interval is 0.0321. There are 24 homozygotes in gnomad4. There are 761 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4 linkuse as main transcript	c.1406C>T	p.Ala469Val	missense_variant	6/6	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.1406C>T	p.Ala469Val	missense_variant	6/6	1	NM_194255.4	ENSP00000308895	A2	P41440-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1615

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00446

AC:

824

AN:

184868

Hom.:

AF XY:

0.00450

AC XY:

451

AN XY:

100328

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.000589

Gnomad EAS exome

AF:

0.000423

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000778

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00211

AC:

3006

AN:

1425966

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

1617

AN XY:

705972

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.00372

Gnomad4 ASJ exome

AF:

0.000318

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000381

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.0106

AC:

1619

AN:

152320

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

761

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0336

Gnomad4 AMR

AF:

0.00594

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0276

AC:

118

ESP6500EA

AF:

0.000603

AC:

ExAC

AF:

0.00443

AC:

519

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.054

Sift

Benign

0.092

T;T

Sift4G

Uncertain

0.054

T;T

Polyphen

0.13

B;.

Vest4

0.019

MVP

0.26

MPC

0.13

ClinPred

0.0092

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.28

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