rs1139266

chr11-45811384-G-Achr11-45811384-G-T

Variant summary

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

The NM_018389.5(SLC35C1):c.*49G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,424,788 control chromosomes in the GnomAD database, including 373,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (29836 hom., cov: 33)
  • Exomes 𝑓: 0.73 (343991 hom.)
• Consequence: SLC35C1 NM_018389.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.197

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=-0.8).
• BP6: Variant 11-45811384-G-A is Benign according to our data. Variant chr11-45811384-G-A is described in ClinVar as [Benign]. Clinvar id is 261026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.*49G>A		3_prime_UTR_variant	2/2	ENST00000314134.4
SLC35C1	NM_001145265.2	c.*49G>A		3_prime_UTR_variant	3/3
SLC35C1	NM_001145266.1	c.*49G>A		3_prime_UTR_variant	3/3
SLC35C1	XM_011520202.3	c.*49G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.*49G>A		3_prime_UTR_variant	2/2	1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.*49G>A		3_prime_UTR_variant	3/3	1		A1
SLC35C1	ENST00000526817.2	c.*49G>A		3_prime_UTR_variant	3/3	2		A1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87521 AN: 151996 Hom.: 29830 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.631 AC: 44783 AN: 71026 Hom.: 15436 AF XY: 0.639 AC XY: 23188 AN XY: 36260

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.809

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.674

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.760

Gnomad OTH exome AF: 0.685

GnomAD4 exome AF: 0.726 AC: 923808 AN: 1272674 Hom.: 343991 Cov.: 23 AF XY: 0.726 AC XY: 449975 AN XY: 619382

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.761

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.576 AC: 87550 AN: 152114 Hom.: 29836 Cov.: 33 AF XY: 0.576 AC XY: 42811 AN XY: 74338

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.609

Alfa AF: 0.723 Hom.: 51908

Bravo AF: 0.551

Asia WGS AF: 0.525 AC: 1828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency type II Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.7
Dann	Benign	0.57

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: rs1139266; hg19: chr11-45832935; COSMIC: COSV58480616; COSMIC: COSV58480616;