NM_194255.4:c.-43C>T

Variant names:

• chr21-45538002-G-A
• rs1131596
• NM_194255.4:c.-43C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_194255.4(SLC19A1):​c.-43C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,437,318 control chromosomes in the GnomAD database, including 221,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20155 hom., cov: 32)
  • Exomes 𝑓: 0.56 (201480 hom.)
• Consequence: SLC19A1 NM_194255.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13
• Publications: 45 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-45538002-G-A is Benign according to our data. Variant chr21-45538002-G-A is described in ClinVar as Benign. ClinVar VariationId is 1220816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 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.-43C>T		5_prime_UTR	Exon 2 of 6	NP_919231.1	P41440-1
	SLC19A1	NM_001352512.2		c.-43C>T		5_prime_UTR	Exon 2 of 6	NP_001339441.1	P41440-1
	SLC19A1	NM_001205206.4		c.-43C>T		5_prime_UTR	Exon 2 of 6	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.-43C>T		5_prime_UTR	Exon 2 of 6	ENSP00000308895.4	P41440-1
	SLC19A1	ENST00000567670.5	TSL:1	c.-43C>T		5_prime_UTR	Exon 2 of 6	ENSP00000457278.1	H3BTQ3
	SLC19A1	ENST00000380010.8	TSL:1	c.-43C>T		5_prime_UTR	Exon 2 of 6	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76469 AN: 151792 Hom.: 20135 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.494

GnomAD2 exomes AF: 0.522 AC: 47113 AN: 90294 AF XY: 0.528

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.442

Gnomad FIN exome AF: 0.524

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.557 AC: 716515 AN: 1285408 Hom.: 201480 Cov.: 22 AF XY: 0.559 AC XY: 349314 AN XY: 625410

African (AFR) AF: 0.320 AC: 9274 AN: 28970

American (AMR) AF: 0.552 AC: 14786 AN: 26772

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 11893 AN: 20224

East Asian (EAS) AF: 0.444 AC: 14891 AN: 33558

South Asian (SAS) AF: 0.584 AC: 39398 AN: 67434

European-Finnish (FIN) AF: 0.546 AC: 17460 AN: 31988

Middle Eastern (MID) AF: 0.489 AC: 2294 AN: 4690

European-Non Finnish (NFE) AF: 0.567 AC: 577306 AN: 1018156

Other (OTH) AF: 0.545 AC: 29213 AN: 53616

GnomAD4 genome AF: 0.504 AC: 76519 AN: 151910 Hom.: 20155 Cov.: 32 AF XY: 0.505 AC XY: 37521 AN XY: 74230

African (AFR) AF: 0.341 AC: 14127 AN: 41414

American (AMR) AF: 0.564 AC: 8621 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2419 AN: 5136

South Asian (SAS) AF: 0.594 AC: 2861 AN: 4820

European-Finnish (FIN) AF: 0.548 AC: 5796 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 140 AN: 290

European-Non Finnish (NFE) AF: 0.571 AC: 38788 AN: 67904

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.536 Hom.: 21085

Bravo AF: 0.497

Asia WGS AF: 0.531 AC: 1844 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1131596; hg19: chr21-46957916; COSMIC: COSV60756726; COSMIC: COSV60756726;