4-138288547-G-T

Position:

• chr4-138288547-G-T

Variant summary

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

The XM_047449956.1(SLC7A11):​c.-236-1735C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,786 control chromosomes in the GnomAD database, including 21,698 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 0.53 (21698 hom., cov: 31)
• Consequence: SLC7A11 XM_047449956.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A11	XM_047449956.1	c.-236-1735C>A		intron_variant			XP_047305912.1
SLC7A11	XM_047449957.1	c.-236-1735C>A		intron_variant			XP_047305913.1
SLC7A11	XM_047449958.1	c.-236-1735C>A		intron_variant			XP_047305914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80960 AN: 151668 Hom.: 21684 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.534 AC: 81026 AN: 151786 Hom.: 21698 Cov.: 31 AF XY: 0.537 AC XY: 39834 AN XY: 74162

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.516

Alfa AF: 0.493 Hom.: 30680

Bravo AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6817763; hg19: chr4-139209701;