rs2146232

Variant names:

• chr14-22787413-G-A
• rs2146232
• NM_003982.4:c.500-7362C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22787413-G-A
• chr14-22787413-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003982.4(SLC7A7):​c.500-7362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 150,930 control chromosomes in the GnomAD database, including 26,343 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 0.58 (26343 hom., cov: 29)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 2 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.500-7362C>T		intron_variant	Intron 2 of 9	ENST00000674313.1	NP_003973.3
SLC7A7	NM_001126105.3	c.500-7362C>T		intron_variant	Intron 3 of 10		NP_001119577.1
SLC7A7	NM_001126106.4	c.500-7362C>T		intron_variant	Intron 3 of 10		NP_001119578.1
SLC7A7	XM_011537299.2	c.500-7362C>T		intron_variant	Intron 2 of 9		XP_011535601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.500-7362C>T		intron_variant	Intron 2 of 9		NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 87720 AN: 150810 Hom.: 26327 Cov.: 29

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.582 AC: 87769 AN: 150930 Hom.: 26343 Cov.: 29 AF XY: 0.586 AC XY: 43182 AN XY: 73692

African (AFR) AF: 0.407 AC: 16741 AN: 41128

American (AMR) AF: 0.676 AC: 10222 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1986 AN: 3458

East Asian (EAS) AF: 0.676 AC: 3447 AN: 5102

South Asian (SAS) AF: 0.679 AC: 3260 AN: 4800

European-Finnish (FIN) AF: 0.676 AC: 7023 AN: 10388

Middle Eastern (MID) AF: 0.643 AC: 184 AN: 286

European-Non Finnish (NFE) AF: 0.636 AC: 43051 AN: 67664

Other (OTH) AF: 0.606 AC: 1267 AN: 2092

Alfa AF: 0.607 Hom.: 3073

Bravo AF: 0.576

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		0.12
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: rs2146232; hg19: chr14-23256622;