14-22780330-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003982.4(SLC7A7):c.500-279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 401,214 control chromosomes in the GnomAD database, including 32,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10879 hom., cov: 32)
  • Exomes 𝑓: 0.41 (21632 hom.)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-22780330-A-G is Benign according to our data. Variant chr14-22780330-A-G is described in ClinVar as [Benign]. Clinvar id is 667492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A7	NM_003982.4	c.500-279T>C		intron_variant		ENST00000674313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A7	ENST00000674313.1	c.500-279T>C		intron_variant			NM_003982.4	P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55938 AN: 151894 Hom.: 10863 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.405 AC: 100934 AN: 249204 Hom.: 21632 Cov.: 2 AF XY: 0.408 AC XY: 54705 AN XY: 134114

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.368 AC: 55998 AN: 152010 Hom.: 10879 Cov.: 32 AF XY: 0.376 AC XY: 27960 AN XY: 74306

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.381

Alfa AF: 0.378 Hom.: 15563

Bravo AF: 0.373

Asia WGS AF: 0.509 AC: 1764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.12
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12433985; hg19: chr14-23249539;