dbSNP rs3815559: SLC7A5:c.1140+85C>G (chr16-87837760-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003486.7(SLC7A5):c.1140+85C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,113,994 control chromosomes in the GnomAD database, including 32,574 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 0.24 ( 4616 hom., cov: 35)

Exomes 𝑓: 0.23 ( 27958 hom. )

Consequence

SLC7A5
NM_003486.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

6 publications found

Variant links:

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A5 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SLC7A5 links:

ENSG00000260466 (HGNC:58301):

ENSG00000260466 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A5	NM_003486.7 link	c.1140+85C>G		intron_variant	Intron 7 of 9	ENST00000261622.5	NP_003477.4	Q01650
SLC7A5-AS1	XR_007065175.1 link	n.*73G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5 link	c.1140+85C>G		intron_variant	Intron 7 of 9	1	NM_003486.7	ENSP00000261622.4		Q01650

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36093

AN:

152140

Hom.:

4600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.0596

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.228

AC:

219111

AN:

961736

Hom.:

27958

Cov.:

AF XY:

0.237

AC XY:

115982

AN XY:

489422

show subpopulations

African (AFR)

AF:

0.277

AC:

6458

AN:

23356

American (AMR)

AF:

0.246

AC:

8586

AN:

34832

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

5966

AN:

22112

East Asian (EAS)

AF:

0.0589

AC:

2015

AN:

34230

South Asian (SAS)

AF:

0.429

AC:

30131

AN:

70246

European-Finnish (FIN)

AF:

0.168

AC:

6947

AN:

41268

Middle Eastern (MID)

AF:

0.355

AC:

1289

AN:

3628

European-Non Finnish (NFE)

AF:

0.215

AC:

147852

AN:

688514

Other (OTH)

AF:

0.227

AC:

9867

AN:

43550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8170

16341

24511

32682

40852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4104

8208

12312

16416

20520

<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:

0.237

AC:

36147

AN:

152258

Hom.:

4616

Cov.:

AF XY:

0.237

AC XY:

17667

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.274

AC:

11383

AN:

41554

American (AMR)

AF:

0.242

AC:

3698

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

856

AN:

3472

East Asian (EAS)

AF:

0.0595

AC:

308

AN:

5176

South Asian (SAS)

AF:

0.420

AC:

2023

AN:

4820

European-Finnish (FIN)

AF:

0.159

AC:

1683

AN:

10618

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15190

AN:

68002

Other (OTH)

AF:

0.235

AC:

497

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1414

2827

4241

5654

7068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.246

Hom.:

572

Bravo

AF:

0.240

Asia WGS

AF:

0.241

AC:

839

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.12

(source)

DANN

Benign

0.53

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over