rs3778504

Positions:

• chr6-44221463-G-A

Variant summary

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

The ENST00000393844.7(SLC29A1):​c.-52+1681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 393,784 control chromosomes in the GnomAD database, including 226 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 0.031 (134 hom., cov: 32)
  • Exomes 𝑓: 0.019 (92 hom.)
• Consequence: SLC29A1 ENST00000393844.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC29A1	NM_001304462.2	c.87-123G>A		intron_variant			NP_001291391.1
SLC29A1	NM_001304465.2	c.24+1681G>A		intron_variant			NP_001291394.1
SLC29A1	NM_001304466.2	c.24+1681G>A		intron_variant			NP_001291395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC29A1	ENST00000393844.7	c.-52+1681G>A		intron_variant		1		ENSP00000377427	P1
SLC29A1	ENST00000371713.6	c.-151-123G>A		intron_variant		5		ENSP00000360778	P1
SLC29A1	ENST00000643028.2	c.-29+1681G>A		intron_variant				ENSP00000495211

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4702 AN: 152174 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.0496

Gnomad SAS AF: 0.0389

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0194 AC: 4680 AN: 241492 Hom.: 92 AF XY: 0.0209 AC XY: 2799 AN XY: 134180

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.00934

Gnomad4 ASJ exome AF: 0.00521

Gnomad4 EAS exome AF: 0.0428

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0309 AC: 4711 AN: 152292 Hom.: 134 Cov.: 32 AF XY: 0.0316 AC XY: 2355 AN XY: 74464

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.0499

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0175 Hom.: 170

Bravo AF: 0.0321

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.65
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs3778504; hg19: chr6-44189200;