Variant 2-64989664-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003038.5(SLC1A4):c.21C>A(p.Thr7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,537,866 control chromosomes in the GnomAD database, including 910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 101 hom., cov: 33)

Exomes 𝑓: 0.012 ( 809 hom. )

Consequence

SLC1A4
NM_003038.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.31

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.2).

BP6

Variant 2-64989664-C-A is Benign according to our data. Variant chr2-64989664-C-A is described in ClinVar as [Benign]. Clinvar id is 1243304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC1A4	NM_003038.5 linkuse as main transcript	c.21C>A	p.Thr7=	synonymous_variant	1/8	ENST00000234256.4
SLC1A4	NM_001193493.2 linkuse as main transcript	c.-134+1044C>A		intron_variant
SLC1A4	NM_001348406.2 linkuse as main transcript	c.-134+1044C>A		intron_variant
SLC1A4	NM_001348407.2 linkuse as main transcript	c.-134+1110C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A4	ENST00000234256.4 linkuse as main transcript	c.21C>A	p.Thr7=	synonymous_variant	1/8	1	NM_003038.5	P1	P43007-1
LINC02245	ENST00000653778.1 linkuse as main transcript	n.513+58290G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2802

AN:

152058

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.0376

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.0289

AC:

5078

AN:

175622

Hom.:

249

AF XY:

0.0313

AC XY:

3109

AN XY:

99326

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0842

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0328

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0123

AC:

17068

AN:

1385692

Hom.:

809

Cov.:

AF XY:

0.0150

AC XY:

10365

AN XY:

689418

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.0820

Gnomad4 ASJ exome

AF:

0.0175

Gnomad4 EAS exome

AF:

0.0234

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.000333

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.0187

GnomAD4 genome

AF:

0.0185

AC:

2808

AN:

152174

Hom.:

101

Cov.:

AF XY:

0.0215

AC XY:

1597

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0700

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.0375

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00331

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00752

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0700

AC:

242

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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

-0.20

CADD

Benign

DANN

Benign

0.96

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