NM_005073.4:c.1446A>G

Variant names:

• chr13-98702500-T-C
• rs8187828
• NM_005073.4:c.1446A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005073.4(SLC15A1):​c.1446A>G​(p.Glu482Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,609,070 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (34 hom.)
• Consequence: SLC15A1 NM_005073.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0600
• Publications: 4 publications found

Genes affected

SLC15A1 (HGNC:10920): (solute carrier family 15 member 1) This gene encodes an intestinal hydrogen peptide cotransporter that is a member of the solute carrier family 15. The encoded protein is localized to the brush border membrane of the intestinal epithelium and mediates the uptake of di- and tripeptides from the lumen into the enterocytes. This protein plays an important role in the uptake and digestion of dietary proteins. This protein also facilitates the absorption of numerous peptidomimetic drugs. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 13-98702500-T-C is Benign according to our data. Variant chr13-98702500-T-C is described in ClinVar as Benign. ClinVar VariationId is 776806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1634/152306) while in subpopulation AFR AF = 0.0378 (1569/41554). AF 95% confidence interval is 0.0362. There are 44 homozygotes in GnomAd4. There are 776 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005073.4. 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
	SLC15A1	NM_005073.4	MANE Select	c.1446A>G	p.Glu482Glu	synonymous	Exon 18 of 23	NP_005064.1	P46059

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A1	ENST00000376503.10	TSL:1 MANE Select	c.1446A>G	p.Glu482Glu	synonymous	Exon 18 of 23	ENSP00000365686.4	P46059
	SLC15A1	ENST00000856774.1		c.1269A>G	p.Glu423Glu	synonymous	Exon 16 of 21	ENSP00000526834.1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1638 AN: 152188 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00286 AC: 718 AN: 250900 AF XY: 0.00225

Gnomad AFR exome AF: 0.0376

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00113 AC: 1644 AN: 1456764 Hom.: 34 Cov.: 28 AF XY: 0.000971 AC XY: 704 AN XY: 725088

African (AFR) AF: 0.0373 AC: 1239 AN: 33248

American (AMR) AF: 0.00188 AC: 84 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00314 AC: 82 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5754

European-Non Finnish (NFE) AF: 0.0000623 AC: 69 AN: 1107638

Other (OTH) AF: 0.00257 AC: 155 AN: 60220

GnomAD4 genome AF: 0.0107 AC: 1634 AN: 152306 Hom.: 44 Cov.: 32 AF XY: 0.0104 AC XY: 776 AN XY: 74474

African (AFR) AF: 0.0378 AC: 1569 AN: 41554

American (AMR) AF: 0.00242 AC: 37 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00552 Hom.: 23

Bravo AF: 0.0123

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.27
DANN	Benign	0.38
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism

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: rs8187828; hg19: chr13-99354754;