14-22780330-A-G

Variant names:

• chr14-22780330-A-G
• rs12433985
• ENST00000554061.5:n.146T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000554061.5(SLC7A7):​n.146T>C variant causes a non coding transcript exon 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 ENST00000554061.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.58
• Publications: 10 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 -20 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 VariationId is 667492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554061.5. 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.500-279T>C		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.500-279T>C		intron	N/A	NP_001119577.1
	SLC7A7	NM_001126106.4		c.500-279T>C		intron	N/A	NP_001119578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000554061.5	TSL:1	n.146T>C		non_coding_transcript_exon	Exon 1 of 9
	SLC7A7	ENST00000674313.1	MANE Select	c.500-279T>C		intron	N/A	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.500-279T>C		intron	N/A	ENSP00000380662.4

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

African (AFR) AF: 0.256 AC: 1886 AN: 7376

American (AMR) AF: 0.578 AC: 6888 AN: 11918

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 2872 AN: 6904

East Asian (EAS) AF: 0.666 AC: 8659 AN: 13008

South Asian (SAS) AF: 0.440 AC: 17574 AN: 39896

European-Finnish (FIN) AF: 0.382 AC: 4244 AN: 11100

Middle Eastern (MID) AF: 0.398 AC: 384 AN: 964

European-Non Finnish (NFE) AF: 0.367 AC: 53142 AN: 144714

Other (OTH) AF: 0.397 AC: 5285 AN: 13324

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

African (AFR) AF: 0.264 AC: 10952 AN: 41468

American (AMR) AF: 0.494 AC: 7547 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3468

East Asian (EAS) AF: 0.642 AC: 3317 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2195 AN: 4826

European-Finnish (FIN) AF: 0.396 AC: 4180 AN: 10550

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24929 AN: 67950

Other (OTH) AF: 0.381 AC: 806 AN: 2116

Alfa AF: 0.377 Hom.: 21510

Bravo AF: 0.373

Asia WGS AF: 0.509 AC: 1764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.64
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12433985; hg19: chr14-23249539;