12-128808722-A-G

Position:

• chr12-128808722-A-G

Variant summary

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

The NM_145648.4(SLC15A4):​c.1258+66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,541,104 control chromosomes in the GnomAD database, including 60,320 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 0.24 (4640 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55680 hom.)
• Consequence: SLC15A4 NM_145648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A4	NM_145648.4	c.1258+66T>C		intron_variant		ENST00000266771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A4	ENST00000266771.10	c.1258+66T>C		intron_variant		1	NM_145648.4	P1
SLC15A4	ENST00000376744.8	c.*210+66T>C		intron_variant, NMD_transcript_variant		2
SLC15A4	ENST00000366292.6	n.1401+66T>C		intron_variant, non_coding_transcript_variant		4
SLC15A4	ENST00000544112.5	n.1132+66T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36424 AN: 152132 Hom.: 4644 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.278 AC: 385604 AN: 1388856 Hom.: 55680 AF XY: 0.282 AC XY: 194523 AN XY: 689426

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.239 AC: 36413 AN: 152248 Hom.: 4640 Cov.: 33 AF XY: 0.236 AC XY: 17578 AN XY: 74426

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.253

Alfa AF: 0.278 Hom.: 6291

Bravo AF: 0.231

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.35

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: rs7311875; hg19: chr12-129293267;