chr11-45805799-A-G

Variant names:

• chr11-45805799-A-G
• rs3808976
• NM_018389.5:c.-3A>G

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.-3A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,612,660 control chromosomes in the GnomAD database, including 39,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6084 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33673 hom.)
• Consequence: SLC35C1 NM_018389.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.745
• Publications: 26 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]

LINC02690 (HGNC:54194): (long intergenic non-protein coding RNA 2690)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-45805799-A-G is Benign according to our data. Variant chr11-45805799-A-G is described in ClinVar as Benign. ClinVar VariationId is 95903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	NM_018389.5	MANE Select	c.-3A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_018389.5	MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 2	NP_060859.4
	SLC35C1	NM_001425155.1		c.-3A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001412084.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-3A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000313318.3
	SLC35C1	ENST00000314134.4	TSL:1 MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 2	ENSP00000313318.3
	SLC35C1	ENST00000442528.2	TSL:1	c.-31-11A>G		intron	N/A	ENSP00000412408.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39871 AN: 152020 Hom.: 6070 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.203 AC: 50541 AN: 249226 AF XY: 0.198

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.209 AC: 305644 AN: 1460522 Hom.: 33673 Cov.: 39 AF XY: 0.206 AC XY: 149905 AN XY: 726548

African (AFR) AF: 0.429 AC: 14343 AN: 33468

American (AMR) AF: 0.132 AC: 5894 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4275 AN: 26136

East Asian (EAS) AF: 0.155 AC: 6143 AN: 39700

South Asian (SAS) AF: 0.146 AC: 12556 AN: 86246

European-Finnish (FIN) AF: 0.280 AC: 14639 AN: 52320

Middle Eastern (MID) AF: 0.129 AC: 729 AN: 5632

European-Non Finnish (NFE) AF: 0.211 AC: 234576 AN: 1111944

Other (OTH) AF: 0.207 AC: 12489 AN: 60354

GnomAD4 genome AF: 0.262 AC: 39928 AN: 152138 Hom.: 6084 Cov.: 32 AF XY: 0.260 AC XY: 19366 AN XY: 74380

African (AFR) AF: 0.416 AC: 17281 AN: 41514

American (AMR) AF: 0.179 AC: 2736 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.136 AC: 701 AN: 5158

South Asian (SAS) AF: 0.150 AC: 725 AN: 4818

European-Finnish (FIN) AF: 0.278 AC: 2946 AN: 10596

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14244 AN: 67970

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.216 Hom.: 3112

Bravo AF: 0.261

Asia WGS AF: 0.155 AC: 540 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.195

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Leukocyte adhesion deficiency type II (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		0.74
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3808976; hg19: chr11-45827350; COSMIC: COSV58480020;