Variant 2-64989609-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003038.5(SLC1A4):c.-35C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 1,448,920 control chromosomes in the GnomAD database, including 1,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 135 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1349 hom. )

Consequence

SLC1A4
NM_003038.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.40

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-64989609-C-T is Benign according to our data. Variant chr2-64989609-C-T is described in ClinVar as [Benign]. Clinvar id is 1288873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SLC1A4	NM_003038.5 linkuse as main transcript	c.-35C>T	5_prime_UTR_variant	1/8	ENST00000234256.4
SLC1A4	NM_001193493.2 linkuse as main transcript	c.-134+989C>T	intron_variant
SLC1A4	NM_001348406.2 linkuse as main transcript	c.-134+989C>T	intron_variant
SLC1A4	NM_001348407.2 linkuse as main transcript	c.-134+1055C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A4	ENST00000234256.4 linkuse as main transcript	c.-35C>T		5_prime_UTR_variant	1/8	1	NM_003038.5	P1	P43007-1
LINC02245	ENST00000653778.1 linkuse as main transcript	n.513+58345G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5080

AN:

152236

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00772

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0521

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0340

AC:

4003

AN:

117808

Hom.:

AF XY:

0.0340

AC XY:

2259

AN XY:

66440

show subpopulations

Gnomad AFR exome

AF:

0.00661

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.0488

Gnomad OTH exome

AF:

0.0340

GnomAD4 exome

AF:

0.0426

AC:

55279

AN:

1296568

Hom.:

1349

Cov.:

AF XY:

0.0421

AC XY:

26949

AN XY:

640130

show subpopulations

Gnomad4 AFR exome

AF:

0.00586

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0000649

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.0484

Gnomad4 OTH exome

AF:

0.0332

GnomAD4 genome

AF:

0.0334

AC:

5082

AN:

152352

Hom.:

135

Cov.:

AF XY:

0.0323

AC XY:

2403

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00769

Gnomad4 AMR

AF:

0.0339

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.0454

Gnomad4 NFE

AF:

0.0521

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0468

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over