chr1-44028880-T-C

Position:

• chr1-44028880-T-C

Variant summary

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

The NM_001024845.3(SLC6A9):​c.-86+2426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,232 control chromosomes in the GnomAD database, including 2,854 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 0.18 (2854 hom., cov: 32)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

Genes affected

SLC6A9 (HGNC:11056): (solute carrier family 6 member 9) The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3	c.-86+2426A>G		intron_variant		ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8	c.-86+2426A>G		intron_variant		5	NM_001024845.3	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27186 AN: 151114 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.180 AC: 27233 AN: 151232 Hom.: 2854 Cov.: 32 AF XY: 0.182 AC XY: 13457 AN XY: 73852

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.192

Alfa AF: 0.149 Hom.: 449

Bravo AF: 0.187

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.64

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: rs783307; hg19: chr1-44494552;