13-29517299-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003045.5(SLC7A1):c.1522A>G(p.Ile508Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,610,986 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I508T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

SLC7A1
NM_003045.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019243956).

BP6

Variant 13-29517299-T-C is Benign according to our data. Variant chr13-29517299-T-C is described in ClinVar as Benign. ClinVar VariationId is 781099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1829/152288) while in subpopulation AFR AF = 0.0424 (1763/41554). AF 95% confidence interval is 0.0408. There are 33 homozygotes in GnomAd4. There are 875 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A1	NM_003045.5	MANE Select	c.1522A>G	p.Ile508Val	missense	Exon 11 of 13	NP_003036.1	P30825

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A1	ENST00000380752.10	TSL:1 MANE Select	c.1522A>G	p.Ile508Val	missense	Exon 11 of 13	ENSP00000370128.5	P30825
SLC7A1	ENST00000936269.1		c.1684A>G	p.Ile562Val	missense	Exon 12 of 14	ENSP00000606328.1
SLC7A1	ENST00000936271.1		c.1546A>G	p.Ile516Val	missense	Exon 11 of 13	ENSP00000606330.1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1826

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

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:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00290

AC:

712

AN:

245916

AF XY:

0.00220

show subpopulations

Gnomad AFR exome

AF:

0.0413

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00115

AC:

1676

AN:

1458698

Hom.:

Cov.:

AF XY:

0.000966

AC XY:

701

AN XY:

725564

show subpopulations

African (AFR)

AF:

0.0438

AC:

1459

AN:

33322

American (AMR)

AF:

0.00150

AC:

AN:

44048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000468

AC:

AN:

85502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1110940

Other (OTH)

AF:

0.00224

AC:

135

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0120

AC:

1829

AN:

152288

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

875

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0424

AC:

1763

AN:

41554

American (AMR)

AF:

0.00359

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0199

Hom.:

2293

Bravo

AF:

0.0136

ESP6500AA

AF:

0.0359

AC:

158

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00371

AC:

451

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.51

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.22

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.020

REVEL

Benign

0.13

Sift

Benign

0.90

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.066

MVP

0.47

MPC

0.64

ClinPred

0.0047

GERP RS

-0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over