2-64997514-A-G

Position:

• chr2-64997514-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003038.5(SLC1A4):​c.528-3934A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,054 control chromosomes in the GnomAD database, including 1,856 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 0.16 (1856 hom., cov: 32)
• Consequence: SLC1A4 NM_003038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A4	NM_003038.5	c.528-3934A>G		intron_variant		ENST00000234256.4	NP_003029.2
SLC1A4	NM_001348406.2	c.-133-3934A>G		intron_variant			NP_001335335.1
SLC1A4	NM_001348407.2	c.-133-3934A>G		intron_variant			NP_001335336.1
SLC1A4	NM_001193493.2	c.-133-3934A>G		intron_variant			NP_001180422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A4	ENST00000234256.4	c.528-3934A>G		intron_variant		1	NM_003038.5	ENSP00000234256.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23748 AN: 151936 Hom.: 1852 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23760 AN: 152054 Hom.: 1856 Cov.: 32 AF XY: 0.156 AC XY: 11603 AN XY: 74320

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0637 Hom.: 69

Bravo AF: 0.157

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.1
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs7592468; hg19: chr2-65224648;