rs12436190

Positions:

• chr14-22788107-A-G
• chr14-22788107-A-T

Variant summary

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

The NM_003982.4(SLC7A7):​c.500-8056T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,074 control chromosomes in the GnomAD database, including 7,898 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 0.31 (7898 hom., cov: 32)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.500-8056T>C		intron_variant		ENST00000674313.1	NP_003973.3
SLC7A7	NM_001126105.3	c.500-8056T>C		intron_variant			NP_001119577.1
SLC7A7	NM_001126106.4	c.500-8056T>C		intron_variant			NP_001119578.1
SLC7A7	XM_011537299.2	c.500-8056T>C		intron_variant			XP_011535601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.500-8056T>C		intron_variant			NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46581 AN: 151954 Hom.: 7865 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.307 AC: 46671 AN: 152074 Hom.: 7898 Cov.: 32 AF XY: 0.309 AC XY: 23000 AN XY: 74340

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.314

Alfa AF: 0.250 Hom.: 5348

Bravo AF: 0.327

Asia WGS AF: 0.440 AC: 1530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.18

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: rs12436190; hg19: chr14-23257316;