14-22801187-T-C

Variant names:

• chr14-22801187-T-C
• rs6572770
• NM_003982.4:c.499+11713A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003982.4(SLC7A7):​c.499+11713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,050 control chromosomes in the GnomAD database, including 45,521 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 0.76 (45521 hom., cov: 30)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 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.499+11713A>G		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.499+11713A>G		intron	N/A	NP_001119577.1
	SLC7A7	NM_001126106.4		c.499+11713A>G		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.499+11713A>G		intron	N/A	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.499+11713A>G		intron	N/A	ENSP00000380662.4
	SLC7A7	ENST00000397529.6	TSL:1	c.499+11713A>G		intron	N/A	ENSP00000380663.2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115934 AN: 151932 Hom.: 45518 Cov.: 30

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.763 AC: 115984 AN: 152050 Hom.: 45521 Cov.: 30 AF XY: 0.760 AC XY: 56443 AN XY: 74300

African (AFR) AF: 0.561 AC: 23273 AN: 41458

American (AMR) AF: 0.835 AC: 12755 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3035 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4136 AN: 5160

South Asian (SAS) AF: 0.831 AC: 3997 AN: 4810

European-Finnish (FIN) AF: 0.734 AC: 7747 AN: 10554

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58303 AN: 68010

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.796 Hom.: 6030

Bravo AF: 0.763

Asia WGS AF: 0.804 AC: 2796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		-0.45
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: rs6572770; hg19: chr14-23270396;