4-138235603-A-G

Position:

• chr4-138235603-A-G

Variant summary

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

The NM_014331.4(SLC7A11):​c.404+722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,114 control chromosomes in the GnomAD database, including 65,193 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 0.92 (65193 hom., cov: 31)
• Consequence: SLC7A11 NM_014331.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A11	NM_014331.4	c.404+722T>C		intron_variant		ENST00000280612.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A11	ENST00000280612.9	c.404+722T>C		intron_variant		1	NM_014331.4	P1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139892 AN: 151996 Hom.: 65170 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.934

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

GnomAD4 genome AF: 0.920 AC: 139967 AN: 152114 Hom.: 65193 Cov.: 31 AF XY: 0.923 AC XY: 68629 AN XY: 74372

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.959

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.936

Alfa AF: 0.937 Hom.: 11030

Bravo AF: 0.909

Asia WGS AF: 0.969 AC: 3364 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.49

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: rs1018278; hg19: chr4-139156757;