11-45805629-C-T

Position:

• chr11-45805629-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018389.5(SLC35C1):​c.-173C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,491,166 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (33 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.329

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=-0.72).
• BP6: Variant 11-45805629-C-T is Benign according to our data. Variant chr11-45805629-C-T is described in ClinVar as [Benign]. Clinvar id is 304734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2087/152296) while in subpopulation AFR AF= 0.047 (1951/41550). AF 95% confidence interval is 0.0452. There are 40 homozygotes in gnomad4. There are 961 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.-173C>T		5_prime_UTR_variant	1/2	ENST00000314134.4
SLC35C1	XM_011520203.4	c.-173C>T		5_prime_UTR_variant	1/2
SLC35C1	NM_001145265.2	c.-31-181C>T		intron_variant
SLC35C1	NM_001145266.1	c.-31-181C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.-173C>T		5_prime_UTR_variant	1/2	1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.-31-181C>T		intron_variant		1		A1
SLC35C1	ENST00000526817.2	c.-31-181C>T		intron_variant		2		A1
SLC35C1	ENST00000530471.1	c.-31-181C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2084 AN: 152178 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00147 AC: 1965 AN: 1338870 Hom.: 33 Cov.: 35 AF XY: 0.00128 AC XY: 840 AN XY: 654006

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.00317

Gnomad4 ASJ exome AF: 0.000223

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000688

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.0137 AC: 2087 AN: 152296 Hom.: 40 Cov.: 32 AF XY: 0.0129 AC XY: 961 AN XY: 74466

Gnomad4 AFR AF: 0.0470

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00972 Hom.: 8

Bravo AF: 0.0157

Asia WGS AF: 0.00318 AC: 11 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 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs78455013; hg19: chr11-45827180;