21-45531642-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_194255.4(SLC19A1):c.696T>C(p.Pro232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,611,988 control chromosomes in the GnomAD database, including 269,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25021 hom., cov: 35)
  • Exomes 𝑓: 0.58 (244663 hom.)
• Consequence: SLC19A1 NM_194255.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.56

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 21-45531642-A-G is Benign according to our data. Variant chr21-45531642-A-G is described in ClinVar as [Benign]. Clinvar id is 1601263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_194255.4	c.696T>C	p.Pro232=	synonymous_variant	3/6	ENST00000311124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000311124.9	c.696T>C	p.Pro232=	synonymous_variant	3/6	1	NM_194255.4	A2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86981 AN: 152064 Hom.: 24974 Cov.: 35

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.542

GnomAD3 exomes AF: 0.578 AC: 142920 AN: 247472 Hom.: 41580 AF XY: 0.582 AC XY: 78349 AN XY: 134530

Gnomad AFR exome AF: 0.548

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.621

Gnomad EAS exome AF: 0.478

Gnomad SAS exome AF: 0.642

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.578 AC: 843586 AN: 1459806 Hom.: 244663 Cov.: 76 AF XY: 0.580 AC XY: 421267 AN XY: 726254

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.579

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.572 AC: 87084 AN: 152182 Hom.: 25021 Cov.: 35 AF XY: 0.571 AC XY: 42515 AN XY: 74398

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.547

Alfa AF: 0.583 Hom.: 15590

Bravo AF: 0.572

Asia WGS AF: 0.564 AC: 1963 AN: 3478

EpiCase AF: 0.574

EpiControl AF: 0.576

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.43
Dann	Benign	0.31

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

Other links and lift over

dbSNP: rs12659; hg19: chr21-46951556; COSMIC: COSV60753605; COSMIC: COSV60753605;