21-45533378-C-T

Variant names:

• chr21-45533378-C-T
• rs2330183
• NM_194255.4:c.190-1230G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194255.4(SLC19A1):​c.190-1230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,054 control chromosomes in the GnomAD database, including 20,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20711 hom., cov: 34)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• immunodeficiency 114, folate-responsive

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• megaloblastic anemia, folate-responsive

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	NM_194255.4	MANE Select	c.190-1230G>A		intron	N/A	NP_919231.1	P41440-1
	SLC19A1	NM_001352512.2		c.190-1230G>A		intron	N/A	NP_001339441.1	P41440-1
	SLC19A1	NM_001205207.3		c.69+1160G>A		intron	N/A	NP_001192136.1	P41440-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.190-1230G>A		intron	N/A	ENSP00000308895.4	P41440-1
	SLC19A1	ENST00000567670.5	TSL:1	c.190-1230G>A		intron	N/A	ENSP00000457278.1	H3BTQ3
	SLC19A1	ENST00000380010.8	TSL:1	c.190-1230G>A		intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77450 AN: 151936 Hom.: 20686 Cov.: 34

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77509 AN: 152054 Hom.: 20711 Cov.: 34 AF XY: 0.511 AC XY: 38001 AN XY: 74336

African (AFR) AF: 0.341 AC: 14153 AN: 41494

American (AMR) AF: 0.567 AC: 8678 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2143 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2419 AN: 5140

South Asian (SAS) AF: 0.604 AC: 2915 AN: 4830

European-Finnish (FIN) AF: 0.557 AC: 5902 AN: 10596

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39462 AN: 67902

Other (OTH) AF: 0.506 AC: 1068 AN: 2112

Alfa AF: 0.558 Hom.: 30381

Bravo AF: 0.502

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.48
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2330183; hg19: chr21-46953292;