rs2240793

Variant names:

• chr5-150203737-T-C
• rs2240793
• NM_014228.5:c.1158T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150203737-T-C
• chr5-150203737-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014228.5(SLC6A7):​c.1158T>C​(p.Phe386Phe) 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
• Publications: 20 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 -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 rank	MANE	Protein	UniProt
SLC6A7	NM_014228.5	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 14	ENST00000230671.7	NP_055043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A7	ENST00000230671.7	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 14	1	NM_014228.5	ENSP00000230671.2
SLC6A7	ENST00000524041.1	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 16	5		ENSP00000428200.1

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

GnomAD2 exomes AF: 0.715 AC: 179226 AN: 250756 AF XY: 0.719

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 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

African (AFR) AF: 0.639 AC: 21205 AN: 33182

American (AMR) AF: 0.775 AC: 34635 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 19480 AN: 26070

East Asian (EAS) AF: 0.465 AC: 18417 AN: 39628

South Asian (SAS) AF: 0.742 AC: 63799 AN: 86008

European-Finnish (FIN) AF: 0.614 AC: 32723 AN: 53338

Middle Eastern (MID) AF: 0.789 AC: 4536 AN: 5752

European-Non Finnish (NFE) AF: 0.769 AC: 848297 AN: 1103798

Other (OTH) AF: 0.739 AC: 44400 AN: 60096

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

African (AFR) AF: 0.643 AC: 26466 AN: 41156

American (AMR) AF: 0.769 AC: 11719 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2616 AN: 3460

East Asian (EAS) AF: 0.487 AC: 2478 AN: 5092

South Asian (SAS) AF: 0.734 AC: 3515 AN: 4786

European-Finnish (FIN) AF: 0.626 AC: 6532 AN: 10436

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51286 AN: 67828

Other (OTH) AF: 0.725 AC: 1529 AN: 2108

Alfa AF: 0.741 Hom.: 35481

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
PhyloP100		0.98
Mutation Taster		=91/9	polymorphism

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