rs4285028

Variant names:

• chr3-121941817-A-C
• rs4285028
• NM_021082.4:c.*810A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-121941817-A-C
• chr3-121941817-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021082.4(SLC15A2):​c.*810A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,152 control chromosomes in the GnomAD database, including 4,546 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 0.22 (4546 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLC15A2 NM_021082.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 50 publications found

Genes affected

SLC15A2 (HGNC:10921): (solute carrier family 15 member 2) The mammalian kidney expresses a proton-coupled peptide transporter that is responsible for the absorption of small peptides, as well as beta-lactam antibiotics and other peptide-like drugs, from the tubular filtrate. This transporter, SLC15A2, belongs to the same gene family as SLC15A1 (MIM 600544), the proton-coupled peptide transporter found in the small intestine (Liu et al, 1995 [PubMed 7756356]).[supplied by OMIM, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A2	NM_021082.4	c.*810A>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000489711.6	NP_066568.3
SLC15A2	NM_001145998.2	c.*810A>C		3_prime_UTR_variant	Exon 21 of 21		NP_001139470.1
SLC15A2	XM_005247722.4	c.*810A>C		3_prime_UTR_variant	Exon 21 of 21		XP_005247779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A2	ENST00000489711.6	c.*810A>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_021082.4	ENSP00000417085.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33800 AN: 152032 Hom.: 4541 Cov.: 32

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.222 AC: 33813 AN: 152150 Hom.: 4546 Cov.: 32 AF XY: 0.224 AC XY: 16676 AN XY: 74358

African (AFR) AF: 0.0946 AC: 3929 AN: 41546

American (AMR) AF: 0.369 AC: 5645 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3470

East Asian (EAS) AF: 0.0669 AC: 347 AN: 5184

South Asian (SAS) AF: 0.162 AC: 781 AN: 4826

European-Finnish (FIN) AF: 0.274 AC: 2890 AN: 10544

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18200 AN: 67982

Other (OTH) AF: 0.253 AC: 536 AN: 2116

Alfa AF: 0.247 Hom.: 17347

Bravo AF: 0.226

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		0.39
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: rs4285028; hg19: chr3-121660664;