chr21-45514912-G-A

Variant names:

• chr21-45514912-G-A
• rs1051298
• NM_194255.4:c.*746C>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.*746C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,285,862 control chromosomes in the GnomAD database, including 130,437 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 0.46 (16600 hom., cov: 33)
  • Exomes 𝑓: 0.45 (113837 hom.)
• Consequence: SLC19A1 NM_194255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 37 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.*746C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.*746C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70592 AN: 151890 Hom.: 16589 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.446 AC: 506192 AN: 1133850 Hom.: 113837 Cov.: 16 AF XY: 0.447 AC XY: 248916 AN XY: 556756

African (AFR) AF: 0.535 AC: 12263 AN: 22932

American (AMR) AF: 0.431 AC: 6318 AN: 14666

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 7270 AN: 18112

East Asian (EAS) AF: 0.577 AC: 17164 AN: 29754

South Asian (SAS) AF: 0.506 AC: 28154 AN: 55620

European-Finnish (FIN) AF: 0.438 AC: 19390 AN: 44228

Middle Eastern (MID) AF: 0.521 AC: 2172 AN: 4168

European-Non Finnish (NFE) AF: 0.437 AC: 391661 AN: 896632

Other (OTH) AF: 0.457 AC: 21800 AN: 47738

GnomAD4 genome AF: 0.465 AC: 70628 AN: 152012 Hom.: 16600 Cov.: 33 AF XY: 0.467 AC XY: 34717 AN XY: 74284

African (AFR) AF: 0.522 AC: 21648 AN: 41468

American (AMR) AF: 0.436 AC: 6673 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3468

East Asian (EAS) AF: 0.553 AC: 2830 AN: 5120

South Asian (SAS) AF: 0.522 AC: 2518 AN: 4822

European-Finnish (FIN) AF: 0.446 AC: 4709 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29335 AN: 67958

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.445 Hom.: 15976

Bravo AF: 0.466

Asia WGS AF: 0.532 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1051298; hg19: chr21-46934826; COSMIC: COSV60589480; COSMIC: COSV60589480;