Genetic Variant SLC7A1:p.Leu417Leu (chr13-29519488-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003045.5(SLC7A1):c.1251C>G(p.Leu417Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,756 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 66 hom. )

Consequence

SLC7A1
NM_003045.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

SLC7A1 (HGNC:11057): (solute carrier family 7 member 1) Enables L-arginine transmembrane transporter activity and L-histidine transmembrane transporter activity. Involved in amino acid transport. Located in membrane. Part of apical plasma membrane; basolateral plasma membrane; and protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 13-29519488-G-C is Benign according to our data. Variant chr13-29519488-G-C is described in ClinVar as [Benign]. Clinvar id is 776789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A1	NM_003045.5 link	c.1251C>G	p.Leu417Leu	synonymous_variant	Exon 9 of 13	ENST00000380752.10	NP_003036.1	P30825A0A024RDQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A1	ENST00000380752.10 link	c.1251C>G	p.Leu417Leu	synonymous_variant	Exon 9 of 13	1	NM_003045.5	ENSP00000370128.5		P30825
SLC7A1	ENST00000473577.1 link	n.23C>G		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2885

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00472

AC:

1186

AN:

251350

Hom.:

AF XY:

0.00356

AC XY:

483

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00181

AC:

2647

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1127

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.0190

AC:

2892

AN:

152238

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1376

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0668

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00545

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.0

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over