1-42952110-C-A

Variant names:

• chr1-42952110-C-A
• rs12407920
• NM_006516.4:c.18+6524G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006516.4(SLC2A1):​c.18+6524G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 346,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 0 publications found

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]

ATP6V0CP4 (HGNC:40002): (ATPase H+ transporting V0 subunit c pseudogene 4)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006516.4. 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
	SLC2A1	NM_006516.4	MANE Select	c.18+6524G>T		intron	N/A	NP_006507.2	P11166

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.18+6524G>T		intron	N/A	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.18+6524G>T		intron	N/A	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.18+6524G>T		intron	N/A	ENSP00000628907.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000288 AC: 1 AN: 346880 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 180016

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10022

American (AMR) AF: 0.00 AC: 0 AN: 11800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11498

East Asian (EAS) AF: 0.00 AC: 0 AN: 25552

South Asian (SAS) AF: 0.00 AC: 0 AN: 25042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2084

European-Non Finnish (NFE) AF: 0.00000467 AC: 1 AN: 213944

Other (OTH) AF: 0.00 AC: 0 AN: 21496

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.21

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: rs12407920; hg19: chr1-43417781;