rs11954180

Variant names:

• chr5-150198406-C-T
• rs11954180
• NM_014228.5:c.585-822C>T

Variant summary

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

The NM_014228.5(SLC6A7):​c.585-822C>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
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	NM_014228.5	MANE Select	c.585-822C>T		intron	N/A	NP_055043.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A7	ENST00000230671.7	TSL:1 MANE Select	c.585-822C>T		intron	N/A	ENSP00000230671.2
	SLC6A7	ENST00000524041.1	TSL:5	c.585-822C>T		intron	N/A	ENSP00000428200.1

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

African (AFR) AF: 0.194 AC: 8069 AN: 41536

American (AMR) AF: 0.0616 AC: 942 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.0447 AC: 216 AN: 4834

European-Finnish (FIN) AF: 0.0341 AC: 362 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0696 AC: 4733 AN: 68028

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0762 Hom.: 316

Bravo AF: 0.106

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11954180; hg19: chr5-149577969;