rs6841268

Variant names:

• chr4-138247487-A-T
• rs6841268
• XM_047449956.1:c.51-5426T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047449956.1(SLC7A11):​c.51-5426T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,542 control chromosomes in the GnomAD database, including 13,099 homozygotes. 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: 𝑓 0.40 (13099 hom., cov: 31)
• Consequence: SLC7A11 XM_047449956.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

Genes affected

SLC7A11 (HGNC:11059): (solute carrier family 7 member 11) This gene encodes a member of a heteromeric, sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate. In this system, designated Xc(-), the anionic form of cysteine is transported in exchange for glutamate. This protein has been identified as the predominant mediator of Kaposi sarcoma-associated herpesvirus fusion and entry permissiveness into cells. Also, increased expression of this gene in primary gliomas (compared to normal brain tissue) was associated with increased glutamate secretion via the XCT channels, resulting in neuronal cell death. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A11	XM_047449956.1	c.51-5426T>A		intron_variant	Intron 5 of 16		XP_047305912.1
SLC7A11	XM_047449957.1	c.51-5426T>A		intron_variant	Intron 6 of 17		XP_047305913.1
SLC7A11	XM_047449958.1	c.51-5426T>A		intron_variant	Intron 6 of 17		XP_047305914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60906 AN: 151424 Hom.: 13092 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 60935 AN: 151542 Hom.: 13099 Cov.: 31 AF XY: 0.399 AC XY: 29542 AN XY: 74052

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.410

Alfa AF: 0.433 Hom.: 1852

Bravo AF: 0.390

Asia WGS AF: 0.418 AC: 1438 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.66
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6841268; hg19: chr4-139168641;