dbSNP rs4646227: SLC15A1:p.Gly419Ala (chr13-98706147-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005073.4(SLC15A1):c.1256G>C(p.Gly419Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,610,572 control chromosomes in the GnomAD database, including 1,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 304 hom., cov: 32)

Exomes 𝑓: 0.027 ( 887 hom. )

Consequence

SLC15A1
NM_005073.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.28

Publications

19 publications found

Variant links:

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]

SLC15A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0015791059).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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.1256G>C	p.Gly419Ala	missense	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.1256G>C	p.Gly419Ala	missense	Exon 16 of 23	ENSP00000365686.4	P46059
	SLC15A1	ENST00000856774.1		c.1079G>C	p.Gly360Ala	missense	Exon 14 of 21	ENSP00000526834.1

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7347

AN:

152106

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0570

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.0795

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0498

GnomAD2 exomes

AF:

0.0377

AC:

9347

AN:

248240

AF XY:

0.0380

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0585

Gnomad EAS exome

AF:

0.0818

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0270

AC:

39394

AN:

1458348

Hom.:

887

Cov.:

AF XY:

0.0281

AC XY:

20349

AN XY:

725210

show subpopulations

African (AFR)

AF:

0.109

AC:

3614

AN:

33240

American (AMR)

AF:

0.0212

AC:

936

AN:

44068

Ashkenazi Jewish (ASJ)

AF:

0.0612

AC:

1597

AN:

26076

East Asian (EAS)

AF:

0.0573

AC:

2271

AN:

39608

South Asian (SAS)

AF:

0.0718

AC:

6111

AN:

85154

European-Finnish (FIN)

AF:

0.00444

AC:

237

AN:

53378

Middle Eastern (MID)

AF:

0.0588

AC:

315

AN:

5358

European-Non Finnish (NFE)

AF:

0.0198

AC:

22001

AN:

1111190

Other (OTH)

AF:

0.0384

AC:

2312

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1715

3429

5144

6858

8573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

956

1912

2868

3824

4780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0485

AC:

7376

AN:

152224

Hom.:

304

Cov.:

AF XY:

0.0471

AC XY:

3509

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.106

AC:

4384

AN:

41504

American (AMR)

AF:

0.0304

AC:

466

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

198

AN:

3472

East Asian (EAS)

AF:

0.0821

AC:

425

AN:

5176

South Asian (SAS)

AF:

0.0792

AC:

382

AN:

4824

European-Finnish (FIN)

AF:

0.00368

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0201

AC:

1364

AN:

68016

Other (OTH)

AF:

0.0483

AC:

102

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

350

701

1051

1402

1752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0284

Hom.:

Bravo

AF:

0.0521

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.111

AC:

490

ESP6500EA

AF:

0.0207

AC:

178

ExAC

AF:

0.0391

AC:

4745

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

EpiCase

AF:

0.0249

EpiControl

AF:

0.0247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0010

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.039

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.36

PhyloP100

-4.3

PrimateAI

Benign

0.25

PROVEAN

Benign

0.50

REVEL

Benign

0.010

Sift

Benign

0.81

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.035

MPC

0.048

ClinPred

0.0025

GERP RS

-9.3

Varity_R

0.024

gMVP

0.48

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over