rs758593

Variant names:

• chr5-150198356-G-A
• rs758593
• NM_014228.5:c.585-872G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014228.5(SLC6A7):​c.585-872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,122 control chromosomes in the GnomAD database, including 26,246 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 0.58 (26246 hom., cov: 33)
• Consequence: SLC6A7 NM_014228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 publications found

Genes affected

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	NM_014228.5	MANE Select	c.585-872G>A		intron	N/A	NP_055043.2	Q99884

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	ENST00000230671.7	TSL:1 MANE Select	c.585-872G>A		intron	N/A	ENSP00000230671.2	Q99884
	SLC6A7	ENST00000524041.1	TSL:5	c.585-872G>A		intron	N/A	ENSP00000428200.1	E5RJL1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88840 AN: 152002 Hom.: 26235 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.584 AC: 88882 AN: 152122 Hom.: 26246 Cov.: 33 AF XY: 0.577 AC XY: 42900 AN XY: 74350

African (AFR) AF: 0.614 AC: 25470 AN: 41490

American (AMR) AF: 0.462 AC: 7054 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2338 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2454 AN: 5166

South Asian (SAS) AF: 0.534 AC: 2572 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5374 AN: 10578

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41487 AN: 68002

Other (OTH) AF: 0.591 AC: 1249 AN: 2112

Alfa AF: 0.596 Hom.: 85874

Bravo AF: 0.580

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.040
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs758593; hg19: chr5-149577919;