rs17050206

Positions:

• chr4-138231464-G-C

Variant summary

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

The NM_014331.4(SLC7A11):​c.520+803C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,158 control chromosomes in the GnomAD database, including 484 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 0.075 (484 hom., cov: 32)
• Consequence: SLC7A11 NM_014331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A11	NM_014331.4	c.520+803C>G		intron_variant		ENST00000280612.9	NP_055146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A11	ENST00000280612.9	c.520+803C>G		intron_variant		1	NM_014331.4	ENSP00000280612	P1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11423 AN: 152040 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0753 AC: 11463 AN: 152158 Hom.: 484 Cov.: 32 AF XY: 0.0777 AC XY: 5779 AN XY: 74382

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0597

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0783 Hom.: 63

Bravo AF: 0.0674

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.68

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: rs17050206; hg19: chr4-139152618;