rs550333679

Variant names:

• chr11-45805145-C-A
• rs550333679
• ENST00000442528.2:c.-32+628C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-45805145-C-A
• chr11-45805145-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_001425155.1(SLC35C1):​c.-219-438C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 986,380 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: SLC35C1 NM_001425155.1 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -3.21
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000743 (113/152066) while in subpopulation AFR AF = 0.00246 (102/41488). AF 95% confidence interval is 0.00207. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425155.1. 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_001425155.1		c.-219-438C>A		intron	N/A	NP_001412084.1	B3KQH0
	SLC35C1	NM_001145265.2		c.-32+628C>A		intron	N/A	NP_001138737.1	Q96A29-2
	SLC35C1	NM_001145266.2		c.-31-665C>A		intron	N/A	NP_001138738.1	Q96A29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C1	ENST00000442528.2	TSL:1	c.-32+628C>A		intron	N/A	ENSP00000412408.2	Q96A29-2
	SLC35C1	ENST00000953729.1		c.-219-438C>A		intron	N/A	ENSP00000623788.1
	SLC35C1	ENST00000526817.2	TSL:2	c.-31-665C>A		intron	N/A	ENSP00000432145.2	Q96A29-2

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 151948 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.0000479 AC: 40 AN: 834314 Hom.: 1 Cov.: 30 AF XY: 0.0000467 AC XY: 18 AN XY: 385404

African (AFR) AF: 0.00165 AC: 26 AN: 15788

American (AMR) AF: 0.000882 AC: 1 AN: 1134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5158

East Asian (EAS) AF: 0.00 AC: 0 AN: 3638

South Asian (SAS) AF: 0.00 AC: 0 AN: 16706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 296

Middle Eastern (MID) AF: 0.000615 AC: 1 AN: 1626

European-Non Finnish (NFE) AF: 0.0000131 AC: 10 AN: 762626

Other (OTH) AF: 0.0000731 AC: 2 AN: 27342

GnomAD4 genome AF: 0.000743 AC: 113 AN: 152066 Hom.: 0 Cov.: 33 AF XY: 0.000619 AC XY: 46 AN XY: 74348

African (AFR) AF: 0.00246 AC: 102 AN: 41488

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67908

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.000722

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-3.2
PromoterAI		0.35	Neutral

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: rs550333679; hg19: chr11-45826696;