NM_194255.4:c.-50+1387G>A

Variant names:

• chr21-45540981-C-T
• rs13050920
• NM_194255.4:c.-50+1387G>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.-50+1387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,956 control chromosomes in the GnomAD database, including 7,927 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 0.31 (7927 hom., cov: 32)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 5 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 = 0.5 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.-50+1387G>A		intron	N/A	NP_919231.1	P41440-1
	SLC19A1	NM_001352512.2		c.-50+806G>A		intron	N/A	NP_001339441.1	P41440-1
	SLC19A1	NM_001205206.4		c.-50+1387G>A		intron	N/A	NP_001192135.1	P41440-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.-50+1387G>A		intron	N/A	ENSP00000308895.4	P41440-1
	SLC19A1	ENST00000567670.5	TSL:1	c.-49-2973G>A		intron	N/A	ENSP00000457278.1	H3BTQ3
	SLC19A1	ENST00000380010.8	TSL:1	c.-50+1387G>A		intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46414 AN: 151838 Hom.: 7921 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.306 AC: 46448 AN: 151956 Hom.: 7927 Cov.: 32 AF XY: 0.314 AC XY: 23288 AN XY: 74266

African (AFR) AF: 0.162 AC: 6707 AN: 41436

American (AMR) AF: 0.379 AC: 5791 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2470 AN: 5150

South Asian (SAS) AF: 0.517 AC: 2484 AN: 4806

European-Finnish (FIN) AF: 0.360 AC: 3793 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22790 AN: 67952

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.322 Hom.: 13901

Bravo AF: 0.299

Asia WGS AF: 0.446 AC: 1555 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	4.0
DANN	Benign	0.74
PhyloP100		1.9
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: rs13050920; hg19: chr21-46960895;