12-128816149-C-T

Position:

• chr12-128816149-C-T

Variant summary

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

The NM_145648.4(SLC15A4):​c.547-1079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,178 control chromosomes in the GnomAD database, including 931 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 0.095 (931 hom., cov: 33)
• Consequence: SLC15A4 NM_145648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A4	NM_145648.4	c.547-1079G>A		intron_variant		ENST00000266771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A4	ENST00000266771.10	c.547-1079G>A		intron_variant		1	NM_145648.4	P1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14394 AN: 152060 Hom.: 921 Cov.: 33

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0947 AC: 14407 AN: 152178 Hom.: 931 Cov.: 33 AF XY: 0.101 AC XY: 7499 AN XY: 74366

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.117

Alfa AF: 0.107 Hom.: 1550

Bravo AF: 0.0972

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.65

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: rs1385374; hg19: chr12-129300694;