NM_003982.4:c.500-8929A>C

Variant names:

• chr14-22788980-T-G
• rs2065134
• NM_003982.4:c.500-8929A>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.500-8929A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,124 control chromosomes in the GnomAD database, including 873 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 0.10 (873 hom., cov: 31)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• 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: 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.500-8929A>C		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.500-8929A>C		intron	N/A	NP_001119577.1
	SLC7A7	NM_001126106.4		c.500-8929A>C		intron	N/A	NP_001119578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.500-8929A>C		intron	N/A	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.500-8929A>C		intron	N/A	ENSP00000380662.4
	SLC7A7	ENST00000397529.6	TSL:1	c.500-8929A>C		intron	N/A	ENSP00000380663.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15705 AN: 152006 Hom.: 874 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0480

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0936

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

GnomAD4 genome AF: 0.103 AC: 15715 AN: 152124 Hom.: 873 Cov.: 31 AF XY: 0.0990 AC XY: 7361 AN XY: 74384

African (AFR) AF: 0.118 AC: 4914 AN: 41480

American (AMR) AF: 0.0755 AC: 1153 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3466

East Asian (EAS) AF: 0.0481 AC: 249 AN: 5180

South Asian (SAS) AF: 0.102 AC: 494 AN: 4828

European-Finnish (FIN) AF: 0.0497 AC: 527 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7765 AN: 67994

Other (OTH) AF: 0.0926 AC: 195 AN: 2106

Alfa AF: 0.105 Hom.: 2659

Bravo AF: 0.105

Asia WGS AF: 0.0700 AC: 241 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	2.1
DANN	Benign	0.95
PhyloP100		-0.48
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: rs2065134; hg19: chr14-23258189;