rs8016634

chr14-22812943-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003982.4(SLC7A7):c.456C>T(p.Phe152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,613,798 control chromosomes in the GnomAD database, including 364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (207 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (157 hom.)
• Consequence: SLC7A7 NM_003982.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.17

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-22812943-G-A is Benign according to our data. Variant chr14-22812943-G-A is described in ClinVar as [Benign]. Clinvar id is 312824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-22812943-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A7	NM_003982.4	c.456C>T	p.Phe152=	synonymous_variant	2/10	ENST00000674313.1
SLC7A7	NM_001126105.3	c.456C>T	p.Phe152=	synonymous_variant	3/11
SLC7A7	NM_001126106.4	c.456C>T	p.Phe152=	synonymous_variant	3/11
SLC7A7	XM_011537299.2	c.456C>T	p.Phe152=	synonymous_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A7	ENST00000674313.1	c.456C>T	p.Phe152=	synonymous_variant	2/10		NM_003982.4	P1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4384 AN: 151896 Hom.: 208 Cov.: 31

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.0231

GnomAD3 exomes AF: 0.00847 AC: 2109 AN: 248878 Hom.: 85 AF XY: 0.00646 AC XY: 870 AN XY: 134744

Gnomad AFR exome AF: 0.0983

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00304

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00394 AC: 5761 AN: 1461784 Hom.: 157 Cov.: 70 AF XY: 0.00357 AC XY: 2597 AN XY: 727192

Gnomad4 AFR exome AF: 0.0977

Gnomad4 AMR exome AF: 0.00626

Gnomad4 ASJ exome AF: 0.00348

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00314

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.00791

GnomAD4 genome AF: 0.0289 AC: 4391 AN: 152014 Hom.: 207 Cov.: 31 AF XY: 0.0276 AC XY: 2049 AN XY: 74310

Gnomad4 AFR AF: 0.0963

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00312

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.0229

Alfa AF: 0.00958 Hom.: 81

Bravo AF: 0.0330

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lysinuric protein intolerance Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.0
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs8016634; hg19: chr14-23282152;