chr12-128808255-T-C

Variant names:

• chr12-128808255-T-C
• rs959987
• NM_145648.4:c.1258+533A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC15A4	NM_145648.4	c.1258+533A>G		intron_variant	Intron 5 of 7	ENST00000266771.10	NP_663623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A4	ENST00000266771.10	c.1258+533A>G		intron_variant	Intron 5 of 7	1	NM_145648.4	ENSP00000266771.5
SLC15A4	ENST00000366292.6	n.1401+533A>G		intron_variant	Intron 3 of 3	4
SLC15A4	ENST00000376744.8	n.*210+533A>G		intron_variant	Intron 4 of 6	2		ENSP00000365935.4
SLC15A4	ENST00000544112.5	n.1132+533A>G		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.567 AC: 23495 AN: 41462

American (AMR) AF: 0.703 AC: 10750 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2815 AN: 3468

East Asian (EAS) AF: 0.772 AC: 3993 AN: 5174

South Asian (SAS) AF: 0.740 AC: 3568 AN: 4824

European-Finnish (FIN) AF: 0.695 AC: 7343 AN: 10566

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51052 AN: 67988

Other (OTH) AF: 0.719 AC: 1515 AN: 2108

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs959987; hg19: chr12-129292800;