11-45805499-G-C

Position:

• chr11-45805499-G-C

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.-303G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,297,856 control chromosomes in the GnomAD database, including 8,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3209 hom., cov: 31)
  • Exomes 𝑓: 0.084 (5604 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0100

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=-0.74).
• BP6: Variant 11-45805499-G-C is Benign according to our data. Variant chr11-45805499-G-C is described in ClinVar as [Benign]. Clinvar id is 304731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.-303G>C		5_prime_UTR_variant	1/2	ENST00000314134.4
SLC35C1	XM_011520203.4	c.-303G>C		5_prime_UTR_variant	1/2
SLC35C1	NM_001145265.2	c.-31-311G>C		intron_variant
SLC35C1	NM_001145266.1	c.-31-311G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.-303G>C		5_prime_UTR_variant	1/2	1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.-31-311G>C		intron_variant		1		A1
SLC35C1	ENST00000526817.2	c.-31-311G>C		intron_variant		2		A1
SLC35C1	ENST00000530471.1	c.-32+183G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24210 AN: 151398 Hom.: 3196 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.00542

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0845 AC: 96816 AN: 1146340 Hom.: 5604 Cov.: 34 AF XY: 0.0819 AC XY: 44947 AN XY: 549096

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.0596

Gnomad4 ASJ exome AF: 0.0720

Gnomad4 EAS exome AF: 0.00323

Gnomad4 SAS exome AF: 0.0218

Gnomad4 FIN exome AF: 0.0912

Gnomad4 NFE exome AF: 0.0831

Gnomad4 OTH exome AF: 0.0830

GnomAD4 genome AF: 0.160 AC: 24261 AN: 151516 Hom.: 3209 Cov.: 31 AF XY: 0.157 AC XY: 11589 AN XY: 74042

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.00544

Gnomad4 SAS AF: 0.0258

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.137

Alfa AF: 0.131 Hom.: 274

Bravo AF: 0.169

Asia WGS AF: 0.0370 AC: 132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency type II Benign:1

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 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	-0.74
CADD	Benign	10
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12289963; hg19: chr11-45827050;