dbSNP rs3796504: SLAMF1:p.Pro333Thr (chr1-160610759-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003037.5(SLAMF1):c.997C>A(p.Pro333Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0803 in 1,611,012 control chromosomes in the GnomAD database, including 5,787 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 0.061 ( 380 hom., cov: 33)

Exomes 𝑓: 0.082 ( 5407 hom. )

Consequence

SLAMF1
NM_003037.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

Publications

32 publications found

Variant links:

Genes affected

SLAMF1 (HGNC:10903): (signaling lymphocytic activation molecule family member 1) Enables SH2 domain binding activity and identical protein binding activity. Involved in several processes, including negative regulation of CD40 signaling pathway; negative regulation of cytokine production; and positive regulation of MAPK cascade. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLAMF1 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=0.0018964708).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF1	NM_003037.5 link	c.997C>A	p.Pro333Thr	missense_variant	Exon 7 of 7	ENST00000302035.11	NP_003028.1	Q13291-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11 link	c.997C>A	p.Pro333Thr	missense_variant	Exon 7 of 7	1	NM_003037.5	ENSP00000306190.6		Q13291-1
SLAMF1	ENST00000538290.2 link	c.*6C>A		downstream_gene_variant		1		ENSP00000438406.2		Q13291-4

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9363

AN:

152186

Hom.:

382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.0547

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0895

Gnomad OTH

AF:

0.0757

GnomAD2 exomes

AF:

0.0699

AC:

17536

AN:

251018

AF XY:

0.0713

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.000871

Gnomad FIN exome

AF:

0.0675

Gnomad NFE exome

AF:

0.0961

Gnomad OTH exome

AF:

0.0818

GnomAD4 exome

AF:

0.0822

AC:

119946

AN:

1458708

Hom.:

5407

Cov.:

AF XY:

0.0819

AC XY:

59451

AN XY:

725792

show subpopulations

African (AFR)

AF:

0.0112

AC:

374

AN:

33442

American (AMR)

AF:

0.0452

AC:

2020

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3151

AN:

26088

East Asian (EAS)

AF:

0.00774

AC:

307

AN:

39686

South Asian (SAS)

AF:

0.0593

AC:

5109

AN:

86202

European-Finnish (FIN)

AF:

0.0713

AC:

3809

AN:

53406

Middle Eastern (MID)

AF:

0.0872

AC:

502

AN:

5758

European-Non Finnish (NFE)

AF:

0.0901

AC:

99955

AN:

1109136

Other (OTH)

AF:

0.0783

AC:

4719

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4763

9527

14290

19054

23817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3520

7040

10560

14080

17600

<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:

0.0614

AC:

9355

AN:

152304

Hom.:

380

Cov.:

AF XY:

0.0607

AC XY:

4519

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0154

AC:

642

AN:

41586

American (AMR)

AF:

0.0616

AC:

942

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3470

East Asian (EAS)

AF:

0.00366

AC:

AN:

5190

South Asian (SAS)

AF:

0.0543

AC:

262

AN:

4826

European-Finnish (FIN)

AF:

0.0666

AC:

706

AN:

10608

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0895

AC:

6089

AN:

68020

Other (OTH)

AF:

0.0750

AC:

158

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

457

914

1370

1827

2284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0836

Hom.:

2759

Bravo

AF:

0.0606

ESP6500AA

AF:

0.0175

AC:

ESP6500EA

AF:

0.0888

AC:

764

ExAC

AF:

0.0719

AC:

8731

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

EpiCase

AF:

0.0927

EpiControl

AF:

0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

3.7

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.2

REVEL

Benign

0.25

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.16

MPC

0.84

ClinPred

0.029

GERP RS

4.1

Varity_R

0.25

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over