17-49705256-C-T

Variant names:

• chr17-49705256-C-T
• rs147270335
• NM_005827.4:c.396G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_005827.4(SLC35B1):​c.396G>A​(p.Leu132Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,168 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (23 hom.)
• Consequence: SLC35B1 NM_005827.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.92

Genes affected

SLC35B1 (HGNC:20798): (solute carrier family 35 member B1) This gene encodes a nucleotide sugar transporter which is a member of solute carrier family 35. The transporters in this family are highly conserved hydrophobic proteins with multiple transmembrane domains. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-49705256-C-T is Benign according to our data. Variant chr17-49705256-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3055762.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.92 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35B1	NM_005827.4	c.396G>A	p.Leu132Leu	synonymous_variant	Exon 5 of 9	ENST00000240333.12	NP_005818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35B1	ENST00000240333.12	c.396G>A	p.Leu132Leu	synonymous_variant	Exon 5 of 9	1	NM_005827.4	ENSP00000240333.8

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00376

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00296 AC: 745 AN: 251396 Hom.: 3 AF XY: 0.00306 AC XY: 416 AN XY: 135878

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00412

Gnomad FIN exome AF: 0.00541

Gnomad NFE exome AF: 0.00392

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00384 AC: 5618 AN: 1461872 Hom.: 23 Cov.: 31 AF XY: 0.00381 AC XY: 2772 AN XY: 727236

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00406

Gnomad4 FIN exome AF: 0.00672

Gnomad4 NFE exome AF: 0.00416

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152296 Hom.: 0 Cov.: 31 AF XY: 0.00208 AC XY: 155 AN XY: 74462

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00443

Gnomad4 NFE AF: 0.00376

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00306 Hom.: 0

Bravo AF: 0.00217

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC35B1-related disorder Benign:1

May 21, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs147270335; hg19: chr17-47782618;