rs1139266

Variant names:

• chr11-45811384-G-A
• rs1139266
• NM_018389.5:c.*49G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-45811384-G-A
• chr11-45811384-G-T

Variant summary

Our verdict is Benign. The variant received -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:5
• Conservation: PhyloP100: -0.197
• Publications: 25 publications found

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]

SLC35C1 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SLC35C1	NM_018389.5	c.*49G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000314134.4	NP_060859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.*49G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_018389.5	ENSP00000313318.3
SLC35C1	ENST00000442528.2	c.*49G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000412408.2
SLC35C1	ENST00000526817.2	c.*49G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000432145.2

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

GnomAD2 exomes AF: 0.631 AC: 44783 AN: 71026 AF XY: 0.639

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 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

African (AFR) AF: 0.182 AC: 5133 AN: 28226

American (AMR) AF: 0.635 AC: 12772 AN: 20102

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 15083 AN: 18860

East Asian (EAS) AF: 0.312 AC: 11053 AN: 35424

South Asian (SAS) AF: 0.679 AC: 42902 AN: 63152

European-Finnish (FIN) AF: 0.704 AC: 21589 AN: 30664

Middle Eastern (MID) AF: 0.738 AC: 2643 AN: 3582

European-Non Finnish (NFE) AF: 0.761 AC: 775754 AN: 1019550

Other (OTH) AF: 0.694 AC: 36879 AN: 53114

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

African (AFR) AF: 0.206 AC: 8544 AN: 41502

American (AMR) AF: 0.635 AC: 9711 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2753 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1688 AN: 5134

South Asian (SAS) AF: 0.654 AC: 3155 AN: 4826

European-Finnish (FIN) AF: 0.737 AC: 7803 AN: 10584

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51682 AN: 67994

Other (OTH) AF: 0.609 AC: 1286 AN: 2110

Alfa AF: 0.699 Hom.: 69143

Bravo AF: 0.551

Asia WGS AF: 0.525 AC: 1828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency type II Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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