Genetic Variant NM_003038.5: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC1A4	NM_003038.5 link	c.528-346T>C	intron_variant	Intron 1 of 7	ENST00000234256.4	NP_003029.2
SLC1A4	NM_001348406.2 link	c.-133-346T>C	intron_variant	Intron 1 of 7		NP_001335335.1
SLC1A4	NM_001348407.2 link	c.-133-346T>C	intron_variant	Intron 1 of 7		NP_001335336.1
SLC1A4	NM_001193493.2 link	c.-133-346T>C	intron_variant	Intron 1 of 6		NP_001180422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A4	ENST00000234256.4 link	c.528-346T>C		intron_variant	Intron 1 of 7	1	NM_003038.5	ENSP00000234256.3		P43007-1

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 v4.3

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

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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