chr6-44231465-C-T

Variant names:

• chr6-44231465-C-T
• rs186556
• NM_001372327.1:c.864+4C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001372327.1(SLC29A1):​c.864+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,578,214 control chromosomes in the GnomAD database, including 203 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (95 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (108 hom.)
• Consequence: SLC29A1 NM_001372327.1 splice_region, intron
• Scores: Splicing: ADA: 0.00006634
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.87
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-44231465-C-T is Benign according to our data. Variant chr6-44231465-C-T is described in ClinVar as Benign. ClinVar VariationId is 780626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372327.1. 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
	SLC29A1	NM_001372327.1	MANE Select	c.864+4C>T		splice_region intron	N/A	NP_001359256.1	Q99808-1
	SLC29A1	NM_001304462.2		c.1101+4C>T		splice_region intron	N/A	NP_001291391.1	Q99808-2
	SLC29A1	NM_001304465.2		c.942+4C>T		splice_region intron	N/A	NP_001291394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A1	ENST00000371755.9	TSL:1 MANE Select	c.864+4C>T		splice_region intron	N/A	ENSP00000360820.3	Q99808-1
	SLC29A1	ENST00000371708.1	TSL:1	c.864+4C>T		splice_region intron	N/A	ENSP00000360773.1	Q99808-1
	SLC29A1	ENST00000393844.7	TSL:1	c.864+4C>T		splice_region intron	N/A	ENSP00000377427.1	Q99808-1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3033 AN: 152092 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00548 AC: 1254 AN: 228916 AF XY: 0.00387

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.00459

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.0000504

Gnomad NFE exome AF: 0.000330

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00222 AC: 3160 AN: 1426004 Hom.: 108 Cov.: 26 AF XY: 0.00190 AC XY: 1348 AN XY: 709630

African (AFR) AF: 0.0717 AC: 2350 AN: 32776

American (AMR) AF: 0.00455 AC: 199 AN: 43738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25562

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39442

South Asian (SAS) AF: 0.000202 AC: 17 AN: 84150

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52634

Middle Eastern (MID) AF: 0.00525 AC: 30 AN: 5716

European-Non Finnish (NFE) AF: 0.000248 AC: 269 AN: 1082922

Other (OTH) AF: 0.00496 AC: 293 AN: 59064

GnomAD4 genome AF: 0.0200 AC: 3039 AN: 152210 Hom.: 95 Cov.: 32 AF XY: 0.0197 AC XY: 1468 AN XY: 74424

African (AFR) AF: 0.0692 AC: 2870 AN: 41492

American (AMR) AF: 0.00647 AC: 99 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68022

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00638 Hom.: 41

Bravo AF: 0.0229

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0050
DANN	Benign	0.43
PhyloP100		-6.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.010		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: rs186556; hg19: chr6-44199202;