chr21-45536657-A-G

Variant names:

• chr21-45536657-A-G
• rs3788200
• NM_194255.4:c.189+1114T>C

Variant summary

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

The NM_194255.4(SLC19A1):​c.189+1114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 165,330 control chromosomes in the GnomAD database, including 24,154 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 0.54 (22279 hom., cov: 33)
  • Exomes 𝑓: 0.52 (1875 hom.)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 21 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.189+1114T>C		intron_variant	Intron 2 of 5	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.189+1114T>C		intron_variant	Intron 2 of 5	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81762 AN: 151938 Hom.: 22238 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.520 AC: 6899 AN: 13274 Hom.: 1875 AF XY: 0.522 AC XY: 3623 AN XY: 6944

African (AFR) AF: 0.360 AC: 103 AN: 286

American (AMR) AF: 0.537 AC: 132 AN: 246

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 235 AN: 400

East Asian (EAS) AF: 0.417 AC: 645 AN: 1548

South Asian (SAS) AF: 0.527 AC: 58 AN: 110

European-Finnish (FIN) AF: 0.519 AC: 853 AN: 1644

Middle Eastern (MID) AF: 0.471 AC: 32 AN: 68

European-Non Finnish (NFE) AF: 0.538 AC: 4458 AN: 8284

Other (OTH) AF: 0.557 AC: 383 AN: 688

GnomAD4 genome AF: 0.538 AC: 81858 AN: 152056 Hom.: 22279 Cov.: 33 AF XY: 0.538 AC XY: 39998 AN XY: 74324

African (AFR) AF: 0.456 AC: 18892 AN: 41448

American (AMR) AF: 0.578 AC: 8852 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2444 AN: 5176

South Asian (SAS) AF: 0.607 AC: 2926 AN: 4820

European-Finnish (FIN) AF: 0.549 AC: 5801 AN: 10560

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38953 AN: 67968

Other (OTH) AF: 0.526 AC: 1110 AN: 2110

Alfa AF: 0.549 Hom.: 27730

Bravo AF: 0.535

Asia WGS AF: 0.551 AC: 1914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.40
PhyloP100		-1.3
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: rs3788200; hg19: chr21-46956571; COSMIC: COSV60756716; COSMIC: COSV60756716;