11-45805010-A-G

Position:

• chr11-45805010-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000442528.2(SLC35C1):​c.-32+493A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 985,680 control chromosomes in the GnomAD database, including 2,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (310 hom., cov: 33)
  • Exomes 𝑓: 0.071 (2209 hom.)
• Consequence: SLC35C1 ENST00000442528.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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=-0.8).
• BP6: Variant 11-45805010-A-G is Benign according to our data. Variant chr11-45805010-A-G is described in ClinVar as [Benign]. Clinvar id is 1292087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35C1	NM_001145265.2	c.-32+493A>G		intron_variant
SLC35C1	NM_001145266.1	c.-32+590A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35C1	ENST00000442528.2	c.-32+493A>G		intron_variant		1		A1
SLC35C1	ENST00000526817.2	c.-32+590A>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7989 AN: 152102 Hom.: 310 Cov.: 33

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0708 AC: 59008 AN: 833460 Hom.: 2209 Cov.: 30 AF XY: 0.0707 AC XY: 27238 AN XY: 384998

Gnomad4 AFR exome AF: 0.00829

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.00165

Gnomad4 SAS exome AF: 0.00758

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0745

Gnomad4 OTH exome AF: 0.0540

GnomAD4 genome AF: 0.0525 AC: 7986 AN: 152220 Hom.: 310 Cov.: 33 AF XY: 0.0518 AC XY: 3859 AN XY: 74436

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0641 Hom.: 41

Bravo AF: 0.0464

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.25
DANN	Benign	0.38

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: rs61884471; hg19: chr11-45826561;