12-128808255-T-C

Variant summary

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

The NM_145648.4(SLC15A4):c.1258+533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,082 control chromosomes in the GnomAD database, including 37,126 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 0.69 (37126 hom., cov: 33)
• Consequence: SLC15A4 NM_145648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

SLC15A4 (HGNC:23090): (solute carrier family 15 member 4) Enables L-histidine transmembrane transporter activity; peptide transmembrane transporter activity; and peptidoglycan transmembrane transporter activity. Involved in several processes, including dipeptide import across plasma membrane; peptidoglycan transport; and positive regulation of toll-like receptor signaling pathway. Located in endolysosome membrane. Is integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A4	NM_145648.4	c.1258+533A>G		intron_variant		ENST00000266771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A4	ENST00000266771.10	c.1258+533A>G		intron_variant		1	NM_145648.4	P1
SLC15A4	ENST00000376744.8	c.*210+533A>G		intron_variant, NMD_transcript_variant		2
SLC15A4	ENST00000366292.6	n.1401+533A>G		intron_variant, non_coding_transcript_variant		4
SLC15A4	ENST00000544112.5	n.1132+533A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105421 AN: 151964 Hom.: 37104 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.694 AC: 105489 AN: 152082 Hom.: 37126 Cov.: 33 AF XY: 0.694 AC XY: 51619 AN XY: 74332

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.719

Alfa AF: 0.700 Hom.: 4670

Bravo AF: 0.688

Asia WGS AF: 0.718 AC: 2497 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	0.24
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs959987; hg19: chr12-129292800;