rs12888930

Variant names:

• chr14-22779374-C-T
• rs12888930
• NM_003982.4:c.626-437G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

SLC7A7 Gene-Disease associations (from GenCC):

• lysinuric protein intolerance

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.626-437G>A		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.626-437G>A		intron	N/A	NP_001119577.1	A0A0S2Z502
	SLC7A7	NM_001126106.4		c.626-437G>A		intron	N/A	NP_001119578.1	Q9UM01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.626-437G>A		intron	N/A	ENSP00000501493.1	Q9UM01
	SLC7A7	ENST00000397528.8	TSL:1	c.626-437G>A		intron	N/A	ENSP00000380662.4	Q9UM01
	SLC7A7	ENST00000397529.6	TSL:1	c.626-437G>A		intron	N/A	ENSP00000380663.2	Q9UM01

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

African (AFR) AF: 0.202 AC: 8389 AN: 41478

American (AMR) AF: 0.485 AC: 7393 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.623 AC: 3214 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4822

European-Finnish (FIN) AF: 0.381 AC: 4017 AN: 10552

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22978 AN: 67978

Other (OTH) AF: 0.352 AC: 743 AN: 2110

Alfa AF: 0.340 Hom.: 26204

Bravo AF: 0.334

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.40
DANN	Benign	0.87
PhyloP100		-1.8
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: rs12888930; hg19: chr14-23248583;