4-138235603-A-G

Variant names:

• chr4-138235603-A-G
• rs1018278
• NM_014331.4:c.404+722T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014331.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A11	NM_014331.4	MANE Select	c.404+722T>C		intron	N/A	NP_055146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A11	ENST00000280612.9	TSL:1 MANE Select	c.404+722T>C		intron	N/A	ENSP00000280612.5

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

African (AFR) AF: 0.754 AC: 31255 AN: 41442

American (AMR) AF: 0.959 AC: 14659 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3435 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5142 AN: 5162

South Asian (SAS) AF: 0.985 AC: 4756 AN: 4828

European-Finnish (FIN) AF: 0.994 AC: 10553 AN: 10612

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 66997 AN: 68002

Other (OTH) AF: 0.936 AC: 1976 AN: 2112

Alfa AF: 0.932 Hom.: 11270

Bravo AF: 0.909

Asia WGS AF: 0.969 AC: 3364 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs1018278; hg19: chr4-139156757;