rs3808976

Positions:

• chr11-45805799-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000442528.2(SLC35C1):​c.-31-11A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,612,660 control chromosomes in the GnomAD database, including 39,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6084 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33673 hom.)
• Consequence: SLC35C1 ENST00000442528.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.745

Genes affected

SLC35C1 (HGNC:20197): (solute carrier family 35 member C1) This gene encodes a GDP-fucose transporter that is found in the Golgi apparatus. Mutations in this gene result in congenital disorder of glycosylation type IIc. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-45805799-A-G is Benign according to our data. Variant chr11-45805799-A-G is described in ClinVar as [Benign]. Clinvar id is 95903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.-3A>G		5_prime_UTR_variant	1/2	ENST00000314134.4
SLC35C1	XM_011520203.4	c.-3A>G		5_prime_UTR_variant	1/2
SLC35C1	NM_001145265.2	c.-31-11A>G		splice_polypyrimidine_tract_variant, intron_variant
SLC35C1	NM_001145266.1	c.-31-11A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.-3A>G		5_prime_UTR_variant	1/2	1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.-31-11A>G		splice_polypyrimidine_tract_variant, intron_variant		1		A1
SLC35C1	ENST00000526817.2	c.-31-11A>G		splice_polypyrimidine_tract_variant, intron_variant		2		A1
SLC35C1	ENST00000530471.1	c.-31-11A>G		splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39871 AN: 152020 Hom.: 6070 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.203 AC: 50541 AN: 249226 Hom.: 5889 AF XY: 0.198 AC XY: 26802 AN XY: 135184

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.209 AC: 305644 AN: 1460522 Hom.: 33673 Cov.: 39 AF XY: 0.206 AC XY: 149905 AN XY: 726548

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.280

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.262 AC: 39928 AN: 152138 Hom.: 6084 Cov.: 32 AF XY: 0.260 AC XY: 19366 AN XY: 74380

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.229

Alfa AF: 0.214 Hom.: 2863

Bravo AF: 0.261

Asia WGS AF: 0.155 AC: 540 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.195

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 04, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Leukocyte adhesion deficiency type II Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3808976; hg19: chr11-45827350; COSMIC: COSV58480020;