Genetic Variant NM_003486.7: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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over