rs7127456

chr11-45810744-A-G

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.536-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,598,348 control chromosomes in the GnomAD database, including 25,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3824 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21696 hom.)
• Consequence: SLC35C1 NM_018389.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.56

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=-0.85).
• BP6: Variant 11-45810744-A-G is Benign according to our data. Variant chr11-45810744-A-G is described in ClinVar as [Benign]. Clinvar id is 261027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_018389.5	c.536-32A>G		intron_variant		ENST00000314134.4
SLC35C1	NM_001145265.2	c.497-32A>G		intron_variant
SLC35C1	NM_001145266.1	c.497-32A>G		intron_variant
SLC35C1	XM_011520202.3	c.29-32A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000314134.4	c.536-32A>G		intron_variant		1	NM_018389.5	P4
SLC35C1	ENST00000442528.2	c.497-32A>G		intron_variant		1		A1
SLC35C1	ENST00000526817.2	c.497-32A>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31747 AN: 151644 Hom.: 3819 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.167 AC: 40554 AN: 242258 Hom.: 4012 AF XY: 0.156 AC XY: 20551 AN XY: 131396

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.0601

Gnomad SAS exome AF: 0.0507

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.166 AC: 240389 AN: 1446586 Hom.: 21696 Cov.: 38 AF XY: 0.161 AC XY: 115568 AN XY: 717636

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0556

Gnomad4 SAS exome AF: 0.0516

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.209 AC: 31784 AN: 151762 Hom.: 3824 Cov.: 33 AF XY: 0.207 AC XY: 15389 AN XY: 74170

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0601

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.184

Alfa AF: 0.177 Hom.: 694

Bravo AF: 0.215

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.023
Dann	Benign	0.23
La Branchor		0.67

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: rs7127456; hg19: chr11-45832295; COSMIC: COSV58481171; COSMIC: COSV58481171;