Genetic Variant SLC1A4:c.528-346T>C (chr2-65001102-T-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_003038.5(SLC1A4):c.528-346T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 204,414 control chromosomes in the GnomAD database, including 5,519 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 0.22 ( 4380 hom., cov: 32)

Exomes 𝑓: 0.18 ( 1139 hom. )

Consequence

SLC1A4
NM_003038.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.639

Publications

8 publications found

Variant links:

Genes affected

SLC1A4 (HGNC:10942): (solute carrier family 1 member 4) The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]

SLC1A4 links:

LINC02245 (HGNC:53134): (long intergenic non-protein coding RNA 2245)

LINC02245 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003038.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC1A4	NM_003038.5	MANE Select	c.528-346T>C	intron	N/A	NP_003029.2
SLC1A4	NM_001348406.2		c.-133-346T>C	intron	N/A	NP_001335335.1
SLC1A4	NM_001348407.2		c.-133-346T>C	intron	N/A	NP_001335336.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A4	ENST00000234256.4	TSL:1 MANE Select	c.528-346T>C	intron	N/A	ENSP00000234256.3	P43007-1
SLC1A4	ENST00000906286.1		c.528-346T>C	intron	N/A	ENSP00000576345.1
SLC1A4	ENST00000906287.1		c.528-346T>C	intron	N/A	ENSP00000576346.1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33245

AN:

152018

Hom.:

4376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.178

AC:

9313

AN:

52278

Hom.:

1139

Cov.:

AF XY:

0.177

AC XY:

4727

AN XY:

26736

show subpopulations

African (AFR)

AF:

0.263

AC:

440

AN:

1674

American (AMR)

AF:

0.339

AC:

609

AN:

1798

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

264

AN:

1882

East Asian (EAS)

AF:

0.530

AC:

1327

AN:

2506

South Asian (SAS)

AF:

0.159

AC:

577

AN:

3628

European-Finnish (FIN)

AF:

0.178

AC:

473

AN:

2658

Middle Eastern (MID)

AF:

0.213

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.143

AC:

4902

AN:

34334

Other (OTH)

AF:

0.188

AC:

664

AN:

3530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

362

724

1085

1447

1809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.219

AC:

33263

AN:

152136

Hom.:

4380

Cov.:

AF XY:

0.223

AC XY:

16616

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.282

AC:

11705

AN:

41470

American (AMR)

AF:

0.301

AC:

4598

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

495

AN:

3470

East Asian (EAS)

AF:

0.553

AC:

2855

AN:

5166

South Asian (SAS)

AF:

0.187

AC:

901

AN:

4826

European-Finnish (FIN)

AF:

0.189

AC:

2000

AN:

10588

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10066

AN:

68002

Other (OTH)

AF:

0.228

AC:

482

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1276

2552

3829

5105

6381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.190

Hom.:

1835

Bravo

AF:

0.237

Asia WGS

AF:

0.350

AC:

1215

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.61

PhyloP100

-0.64

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over