rs1385374

Variant names:

• chr12-128816149-C-T
• rs1385374
• NM_145648.4:c.547-1079G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 59 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	NM_145648.4	MANE Select	c.547-1079G>A		intron	N/A	NP_663623.1	Q8N697-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	ENST00000266771.10	TSL:1 MANE Select	c.547-1079G>A		intron	N/A	ENSP00000266771.5	Q8N697-1
	SLC15A4	ENST00000923390.1		c.697-1079G>A		intron	N/A	ENSP00000593449.1
	SLC15A4	ENST00000964262.1		c.547-1079G>A		intron	N/A	ENSP00000634321.1

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

African (AFR) AF: 0.0214 AC: 889 AN: 41542

American (AMR) AF: 0.197 AC: 3017 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.183 AC: 947 AN: 5174

South Asian (SAS) AF: 0.174 AC: 838 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1219 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6859 AN: 68014

Other (OTH) AF: 0.117 AC: 248 AN: 2116

Alfa AF: 0.103 Hom.: 3347

Bravo AF: 0.0972

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.65
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1385374; hg19: chr12-129300694;