chr21-45532836-T-C

Variant names:

• chr21-45532836-T-C
• rs914232
• NM_194255.4:c.190-688A>G

Variant summary

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

The NM_194255.4(SLC19A1):​c.190-688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,110 control chromosomes in the GnomAD database, including 21,941 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 0.53 (21941 hom., cov: 34)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 12 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

ENSG00000307065 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 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.190-688A>G		intron	N/A	NP_919231.1	P41440-1
	SLC19A1	NM_001352512.2		c.190-688A>G		intron	N/A	NP_001339441.1	P41440-1
	SLC19A1	NM_001205207.3		c.70-688A>G		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.190-688A>G		intron	N/A	ENSP00000308895.4	P41440-1
	SLC19A1	ENST00000567670.5	TSL:1	c.190-688A>G		intron	N/A	ENSP00000457278.1	H3BTQ3
	SLC19A1	ENST00000380010.8	TSL:1	c.190-688A>G		intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80750 AN: 151992 Hom.: 21912 Cov.: 34

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.531 AC: 80826 AN: 152110 Hom.: 21941 Cov.: 34 AF XY: 0.532 AC XY: 39563 AN XY: 74360

African (AFR) AF: 0.412 AC: 17080 AN: 41490

American (AMR) AF: 0.577 AC: 8822 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2436 AN: 5160

South Asian (SAS) AF: 0.616 AC: 2974 AN: 4826

European-Finnish (FIN) AF: 0.557 AC: 5887 AN: 10574

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39587 AN: 67984

Other (OTH) AF: 0.524 AC: 1109 AN: 2116

Alfa AF: 0.568 Hom.: 67647

Bravo AF: 0.526

Asia WGS AF: 0.544 AC: 1890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.41
PhyloP100		-1.5
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: rs914232; hg19: chr21-46952750;