14-22776092-T-C

Variant names:

• chr14-22776092-T-C
• rs3850290
• NM_003982.4:c.894+103A>G

Variant summary

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

The NM_003982.4(SLC7A7):​c.894+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,523,346 control chromosomes in the GnomAD database, including 322,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (25895 hom., cov: 31)
  • Exomes 𝑓: 0.65 (296492 hom.)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.142
• Publications: 7 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=-0.82).
• BP6: Variant 14-22776092-T-C is Benign according to our data. Variant chr14-22776092-T-C is described in ClinVar as Benign. ClinVar VariationId is 1292095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.894+103A>G		intron_variant	Intron 5 of 9	ENST00000674313.1	NP_003973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.894+103A>G		intron_variant	Intron 5 of 9		NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83375 AN: 151870 Hom.: 25881 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.652 AC: 893723 AN: 1371358 Hom.: 296492 Cov.: 22 AF XY: 0.654 AC XY: 449277 AN XY: 687224

African (AFR) AF: 0.212 AC: 6758 AN: 31930

American (AMR) AF: 0.783 AC: 34929 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 17889 AN: 25504

East Asian (EAS) AF: 0.816 AC: 32053 AN: 39298

South Asian (SAS) AF: 0.669 AC: 56287 AN: 84154

European-Finnish (FIN) AF: 0.625 AC: 33343 AN: 53314

Middle Eastern (MID) AF: 0.683 AC: 3833 AN: 5616

European-Non Finnish (NFE) AF: 0.652 AC: 671304 AN: 1029588

Other (OTH) AF: 0.651 AC: 37327 AN: 57372

GnomAD4 genome AF: 0.549 AC: 83398 AN: 151988 Hom.: 25895 Cov.: 31 AF XY: 0.553 AC XY: 41071 AN XY: 74274

African (AFR) AF: 0.230 AC: 9527 AN: 41466

American (AMR) AF: 0.705 AC: 10754 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2421 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4230 AN: 5162

South Asian (SAS) AF: 0.669 AC: 3217 AN: 4812

European-Finnish (FIN) AF: 0.613 AC: 6488 AN: 10578

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44781 AN: 67920

Other (OTH) AF: 0.596 AC: 1258 AN: 2110

Alfa AF: 0.632 Hom.: 76985

Bravo AF: 0.543

Asia WGS AF: 0.722 AC: 2511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		-0.14
PromoterAI		0.0072	Neutral
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: rs3850290; hg19: chr14-23245301;