rs8187836

Variant names:

• chr13-98706224-G-A
• rs8187836
• NM_005073.4:c.1179C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-98706224-G-A
• chr13-98706224-G-T

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.1179C>T​(p.Asn393Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,230 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (19 hom.)
• Consequence: SLC15A1 NM_005073.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39
• Publications: 5 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=-0.89).
• BP6: Variant 13-98706224-G-A is Benign according to our data. Variant chr13-98706224-G-A is described in ClinVar as Benign. ClinVar VariationId is 776807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00824 (1255/152248) while in subpopulation AFR AF = 0.0287 (1192/41526). AF 95% confidence interval is 0.0274. There are 27 homozygotes in GnomAd4. There are 597 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 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.1179C>T	p.Asn393Asn	synonymous	Exon 16 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.1179C>T	p.Asn393Asn	synonymous	Exon 16 of 23	ENSP00000365686.4	P46059
	SLC15A1	ENST00000856774.1		c.1002C>T	p.Asn334Asn	synonymous	Exon 14 of 21	ENSP00000526834.1

Frequencies

GnomAD3 genomes AF: 0.00824 AC: 1253 AN: 152130 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00224 AC: 560 AN: 250384 AF XY: 0.00180

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000933 AC: 1363 AN: 1460982 Hom.: 19 Cov.: 31 AF XY: 0.000791 AC XY: 575 AN XY: 726774

African (AFR) AF: 0.0299 AC: 1000 AN: 33422

American (AMR) AF: 0.00135 AC: 60 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00314 AC: 82 AN: 26126

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39654

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86056

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

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5744

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111628

Other (OTH) AF: 0.00196 AC: 118 AN: 60348

GnomAD4 genome AF: 0.00824 AC: 1255 AN: 152248 Hom.: 27 Cov.: 32 AF XY: 0.00802 AC XY: 597 AN XY: 74432

African (AFR) AF: 0.0287 AC: 1192 AN: 41526

American (AMR) AF: 0.00216 AC: 33 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68016

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00307 Hom.: 15

Bravo AF: 0.00947

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

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	-0.89
CADD	Benign	0.17
DANN	Benign	0.45
PhyloP100		-1.4
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: rs8187836; hg19: chr13-99358478;