rs7127456

Variant names:

• chr11-45810744-A-G
• rs7127456
• NM_018389.5:c.536-32A>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.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 (★★). There are indicators that this mutation may affect the branch point..

• 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:3
• Conservation: PhyloP100: -4.56
• Publications: 9 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 VariationId 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 rank	MANE	Protein	UniProt
SLC35C1	NM_018389.5	c.536-32A>G		intron_variant	Intron 1 of 1	ENST00000314134.4	NP_060859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35C1	ENST00000314134.4	c.536-32A>G		intron_variant	Intron 1 of 1	1	NM_018389.5	ENSP00000313318.3
SLC35C1	ENST00000442528.2	c.497-32A>G		intron_variant	Intron 2 of 2	1		ENSP00000412408.2
SLC35C1	ENST00000526817.2	c.497-32A>G		intron_variant	Intron 2 of 2	2		ENSP00000432145.2

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

GnomAD2 exomes AF: 0.167 AC: 40554 AN: 242258 AF XY: 0.156

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 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

African (AFR) AF: 0.327 AC: 10875 AN: 33272

American (AMR) AF: 0.228 AC: 10085 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3142 AN: 25738

East Asian (EAS) AF: 0.0556 AC: 2192 AN: 39400

South Asian (SAS) AF: 0.0516 AC: 4424 AN: 85676

European-Finnish (FIN) AF: 0.230 AC: 11360 AN: 49408

Middle Eastern (MID) AF: 0.0683 AC: 372 AN: 5444

European-Non Finnish (NFE) AF: 0.171 AC: 188195 AN: 1103742

Other (OTH) AF: 0.163 AC: 9744 AN: 59748

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

African (AFR) AF: 0.316 AC: 13061 AN: 41370

American (AMR) AF: 0.216 AC: 3290 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3466

East Asian (EAS) AF: 0.0601 AC: 309 AN: 5144

South Asian (SAS) AF: 0.0530 AC: 255 AN: 4808

European-Finnish (FIN) AF: 0.223 AC: 2354 AN: 10556

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11535 AN: 67846

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.183 Hom.: 1115

Bravo AF: 0.215

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	-0.85
CADD	Benign	0.023
DANN	Benign	0.23
PhyloP100		-4.6
La Branchor		0.67
BranchPoint Hunter		3.0
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: rs7127456; hg19: chr11-45832295; COSMIC: COSV58481171; COSMIC: COSV58481171;