rs12888930

Positions:

• chr14-22779374-C-T

Variant summary

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

The NM_003982.4(SLC7A7):​c.626-437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,024 control chromosomes in the GnomAD database, including 9,329 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 0.33 (9329 hom., cov: 32)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

SLC7A7 (HGNC:11065): (solute carrier family 7 member 7) The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.626-437G>A		intron_variant		ENST00000674313.1	NP_003973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.626-437G>A		intron_variant			NM_003982.4	ENSP00000501493	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50346 AN: 151906 Hom.: 9316 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.331 AC: 50380 AN: 152024 Hom.: 9329 Cov.: 32 AF XY: 0.340 AC XY: 25247 AN XY: 74308

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.352

Alfa AF: 0.344 Hom.: 9542

Bravo AF: 0.334

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.40
DANN	Benign	0.87

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: rs12888930; hg19: chr14-23248583;