rs12436190

Variant names:

• chr14-22788107-A-G
• rs12436190
• NM_003982.4:c.500-8056T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

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.500-8056T>C		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.500-8056T>C		intron	N/A	NP_001119577.1	A0A0S2Z502
	SLC7A7	NM_001126106.4		c.500-8056T>C		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.500-8056T>C		intron	N/A	ENSP00000501493.1	Q9UM01
	SLC7A7	ENST00000397528.8	TSL:1	c.500-8056T>C		intron	N/A	ENSP00000380662.4	Q9UM01
	SLC7A7	ENST00000397529.6	TSL:1	c.500-8056T>C		intron	N/A	ENSP00000380663.2	Q9UM01

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

African (AFR) AF: 0.403 AC: 16721 AN: 41454

American (AMR) AF: 0.375 AC: 5726 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3101 AN: 5170

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2469 AN: 10586

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15614 AN: 67986

Other (OTH) AF: 0.314 AC: 661 AN: 2108

Alfa AF: 0.257 Hom.: 8811

Bravo AF: 0.327

Asia WGS AF: 0.440 AC: 1530 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.18
PhyloP100		-2.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12436190;

hg19: chr14-23257316;