11-45805170-G-A

Position:

• chr11-45805170-G-A

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.-632G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 990,580 control chromosomes in the GnomAD database, including 4,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1756 hom., cov: 33)
  • Exomes 𝑓: 0.069 (2562 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.04

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=-0.7).
• BP6: Variant 11-45805170-G-A is Benign according to our data. Variant chr11-45805170-G-A is described in ClinVar as [Benign]. Clinvar id is 304724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35C1	NM_018389.5	c.-632G>A		5_prime_UTR_variant	1/2	ENST00000314134.4	NP_060859.4
SLC35C1	XM_011520203.4	c.-632G>A		5_prime_UTR_variant	1/2		XP_011518505.1
SLC35C1	NM_001145265.2	c.-31-640G>A		intron_variant			NP_001138737.1
SLC35C1	NM_001145266.1	c.-31-640G>A		intron_variant			NP_001138738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.-632G>A		5_prime_UTR_variant	1/2	1	NM_018389.5	ENSP00000313318	P4
SLC35C1	ENST00000442528.2	c.-31-640G>A		intron_variant		1		ENSP00000412408	A1
SLC35C1	ENST00000530471.1	c.-178G>A		5_prime_UTR_variant	1/2	3		ENSP00000432669
SLC35C1	ENST00000526817.2	c.-31-640G>A		intron_variant		2		ENSP00000432145	A1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18636 AN: 151966 Hom.: 1756 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0691 AC: 57940 AN: 838496 Hom.: 2562 Cov.: 31 AF XY: 0.0683 AC XY: 26492 AN XY: 387676

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.0614

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0626

Gnomad4 OTH exome AF: 0.0925

GnomAD4 genome AF: 0.123 AC: 18653 AN: 152084 Hom.: 1756 Cov.: 33 AF XY: 0.126 AC XY: 9375 AN XY: 74346

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0910 Hom.: 119

Bravo AF: 0.138

Asia WGS AF: 0.235 AC: 813 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.3
DANN	Benign	0.89
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: rs77254044; hg19: chr11-45826721;