dbSNP rs1044303: SMLR1:p.Val62Met (chr6-130827597-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001195597.2(SMLR1):c.184G>A(p.Val62Met) variant causes a missense change. The variant allele was found at a frequency of 0.33 in 1,535,464 control chromosomes in the GnomAD database, including 89,532 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 0.37 ( 11134 hom., cov: 31)

Exomes 𝑓: 0.33 ( 78398 hom. )

Consequence

SMLR1
NM_001195597.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Publications

26 publications found

Variant links:

Genes affected

SMLR1 (HGNC:44670): (small leucine rich protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMLR1 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=6.7580086E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMLR1	NM_001195597.2 link	c.184G>A	p.Val62Met	missense_variant	Exon 1 of 2	ENST00000541421.2	NP_001182526.1	H3BR10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMLR1	ENST00000541421.2 link	c.184G>A	p.Val62Met	missense_variant	Exon 1 of 2	1	NM_001195597.2	ENSP00000456026.1		H3BR10

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56306

AN:

151648

Hom.:

11119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.650

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.347

GnomAD2 exomes

AF:

0.397

AC:

54294

AN:

136896

AF XY:

0.394

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.326

AC:

450885

AN:

1383698

Hom.:

78398

Cov.:

AF XY:

0.329

AC XY:

224372

AN XY:

682798

show subpopulations

African (AFR)

AF:

0.437

AC:

13814

AN:

31584

American (AMR)

AF:

0.500

AC:

17864

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

5816

AN:

25176

East Asian (EAS)

AF:

0.646

AC:

23070

AN:

35734

South Asian (SAS)

AF:

0.478

AC:

37914

AN:

79236

European-Finnish (FIN)

AF:

0.406

AC:

13765

AN:

33902

Middle Eastern (MID)

AF:

0.260

AC:

1480

AN:

5694

European-Non Finnish (NFE)

AF:

0.294

AC:

317229

AN:

1078776

Other (OTH)

AF:

0.344

AC:

19933

AN:

57898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

17318

34636

51953

69271

86589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10966

21932

32898

43864

54830

<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:

0.371

AC:

56360

AN:

151766

Hom.:

11134

Cov.:

AF XY:

0.380

AC XY:

28185

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.432

AC:

17841

AN:

41328

American (AMR)

AF:

0.436

AC:

6636

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.650

AC:

3347

AN:

5148

South Asian (SAS)

AF:

0.487

AC:

2340

AN:

4800

European-Finnish (FIN)

AF:

0.421

AC:

4439

AN:

10540

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19854

AN:

67934

Other (OTH)

AF:

0.350

AC:

737

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1724

3448

5171

6895

8619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.315

Hom.:

26382

Bravo

AF:

0.376

TwinsUK

AF:

0.308

AC:

1142

ALSPAC

AF:

0.292

AC:

1126

ExAC

AF:

0.337

AC:

5946

Asia WGS

AF:

0.576

AC:

1999

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.076

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0000068

MutationAssessor

Benign

0.81

PhyloP100

4.5

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.0

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.15

GERP RS

5.2

PromoterAI

-0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.12

Mutation Taster

=61/39

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over