chr21-45517044-G-A

Variant names:

• chr21-45517044-G-A
• rs3788190
• NM_194255.4:c.1294-904C>T

Variant summary

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

The NM_194255.4(SLC19A1):​c.1294-904C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,758 control chromosomes in the GnomAD database, including 14,899 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 0.44 (14899 hom., cov: 33)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 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.1294-904C>T		intron	N/A	NP_919231.1	P41440-1
	SLC19A1	NM_001352512.2		c.1294-904C>T		intron	N/A	NP_001339441.1	P41440-1
	SLC19A1	NM_001205207.3		c.1174-904C>T		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.1294-904C>T		intron	N/A	ENSP00000308895.4	P41440-1
	SLC19A1	ENST00000567670.5	TSL:1	c.1293+8773C>T		intron	N/A	ENSP00000457278.1	H3BTQ3
	SLC19A1	ENST00000380010.8	TSL:1	c.1294-1892C>T		intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67195 AN: 151640 Hom.: 14891 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.443 AC: 67217 AN: 151758 Hom.: 14899 Cov.: 33 AF XY: 0.446 AC XY: 33047 AN XY: 74148

African (AFR) AF: 0.457 AC: 18911 AN: 41394

American (AMR) AF: 0.427 AC: 6520 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2845 AN: 5122

South Asian (SAS) AF: 0.481 AC: 2317 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4654 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.429 AC: 29124 AN: 67852

Other (OTH) AF: 0.465 AC: 978 AN: 2104

Alfa AF: 0.439 Hom.: 28281

Bravo AF: 0.444

Asia WGS AF: 0.507 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.61
PhyloP100		-0.097
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: rs3788190; hg19: chr21-46936958;