rs2240793

chr5-150203737-T-Cchr5-150203737-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014228.5(SLC6A7):c.1158T>C(p.Phe386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,603,854 control chromosomes in the GnomAD database, including 449,061 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 0.71 (38295 hom., cov: 28)
  • Exomes 𝑓: 0.75 (410766 hom.)
• Consequence: SLC6A7 NM_014228.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.978 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A7	NM_014228.5	c.1158T>C	p.Phe386=	synonymous_variant	9/14	ENST00000230671.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A7	ENST00000230671.7	c.1158T>C	p.Phe386=	synonymous_variant	9/14	1	NM_014228.5	P1
SLC6A7	ENST00000524041.1	c.1158T>C	p.Phe386=	synonymous_variant	9/16	5

Frequencies

GnomAD3 genomes AF: 0.707 AC: 106948 AN: 151198 Hom.: 38265 Cov.: 28

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.726

GnomAD3 exomes AF: 0.715 AC: 179226 AN: 250756 Hom.: 64854 AF XY: 0.719 AC XY: 97449 AN XY: 135562

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.481

Gnomad SAS exome AF: 0.741

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.753

Gnomad OTH exome AF: 0.725

GnomAD4 exome AF: 0.749 AC: 1087492 AN: 1452538 Hom.: 410766 Cov.: 35 AF XY: 0.749 AC XY: 541646 AN XY: 723084

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.747

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.614

Gnomad4 NFE exome AF: 0.769

Gnomad4 OTH exome AF: 0.739

GnomAD4 genome AF: 0.707 AC: 107040 AN: 151316 Hom.: 38295 Cov.: 28 AF XY: 0.704 AC XY: 52014 AN XY: 73896

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.725

Alfa AF: 0.740 Hom.: 26207

Bravo AF: 0.713

Asia WGS AF: 0.662 AC: 2299 AN: 3476

EpiCase AF: 0.768

EpiControl AF: 0.765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	9.7
Dann	Benign	0.53

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: rs2240793; hg19: chr5-149583300; COSMIC: COSV57938896;