rs11954180

chr5-150198406-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014228.5(SLC6A7):c.585-822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152,296 control chromosomes in the GnomAD database, including 1,041 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 0.099 (1041 hom., cov: 32)
• Consequence: SLC6A7 NM_014228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A7	NM_014228.5	c.585-822C>T		intron_variant		ENST00000230671.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A7	ENST00000230671.7	c.585-822C>T		intron_variant		1	NM_014228.5	P1
SLC6A7	ENST00000524041.1	c.585-822C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15066 AN: 152178 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0802

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

GnomAD4 genome AF: 0.0990 AC: 15070 AN: 152296 Hom.: 1041 Cov.: 32 AF XY: 0.0939 AC XY: 6995 AN XY: 74484

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0757 Hom.: 285

Bravo AF: 0.106

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.8
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11954180; hg19: chr5-149577969;