rs731780

Positions:

• chr6-44225969-C-G
• chr6-44225969-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372327.1(SLC29A1):​c.-51-1294C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 231,858 control chromosomes in the GnomAD database, including 132 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 0.023 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (10 hom.)
• Consequence: SLC29A1 NM_001372327.1 intron
• Scores: Splicing: ADA: 0.00002255
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

Genes affected

SLC29A1 (HGNC:11003): (solute carrier family 29 member 1 (Augustine blood group)) This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylthioinosine (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001372327.1	c.-51-1294C>G		intron_variant		ENST00000371755.9	NP_001359256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000371755.9	c.-51-1294C>G		intron_variant		1	NM_001372327.1	ENSP00000360820	P1

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3541 AN: 152112 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00212 AC: 169 AN: 79628 Hom.: 10 Cov.: 1 AF XY: 0.00195 AC XY: 75 AN XY: 38378

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.00126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000960

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.0234 AC: 3557 AN: 152230 Hom.: 122 Cov.: 32 AF XY: 0.0229 AC XY: 1703 AN XY: 74440

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0179 Hom.: 14

Bravo AF: 0.0270

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.33
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs731780; hg19: chr6-44193706;