chr1-42929202-AG-A

Variant names:

• chr1-42929202-AG-A
• rs531385270
• NM_006516.4:c.972+7delC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS1

The NM_006516.4(SLC2A1):​c.972+7delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,612,434 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: SLC2A1 NM_006516.4 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:6
• Conservation: PhyloP100: 0.874

Genes affected

SLC2A1 (HGNC:11005): (solute carrier family 2 member 1) This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. Mutations in this gene have been found in a family with paroxysmal exertion-induced dyskinesia. [provided by RefSeq, Apr 2013]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 1-42929202-AG-A is Benign according to our data. Variant chr1-42929202-AG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 198543.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Benign=1, Likely_benign=2}. Variant chr1-42929202-AG-A is described in Lovd as [Likely_benign]. Variant chr1-42929202-AG-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000402 (587/1460122) while in subpopulation NFE AF= 0.000515 (572/1110456). AF 95% confidence interval is 0.00048. There are 0 homozygotes in gnomad4_exome. There are 279 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4	c.972+7delC		splice_region_variant, intron_variant	Intron 7 of 9	ENST00000426263.10	NP_006507.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A1	ENST00000426263.10	c.972+7delC		splice_region_variant, intron_variant	Intron 7 of 9	1	NM_006516.4	ENSP00000416293.2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00

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: 0.000279

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000203 AC: 51 AN: 250866 Hom.: 0 AF XY: 0.000221 AC XY: 30 AN XY: 135588

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000402 AC: 587 AN: 1460122 Hom.: 0 Cov.: 31 AF XY: 0.000384 AC XY: 279 AN XY: 726456

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000515

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74472

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000219

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3 Benign:6

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 20, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2013	The variant is found in EPILEPSY panel(s). -

Dystonic disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

GLUT1 deficiency syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

GLUT1 deficiency syndrome 1, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs531385270; hg19: chr1-43394873;