dbSNP rs12076998: SLAMF1:c.-33C>T (chr1-160646978-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_003037.5(SLAMF1):c.-33C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,227,172 control chromosomes in the GnomAD database, including 2,883 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 0.071 ( 427 hom., cov: 31)

Exomes 𝑓: 0.064 ( 2456 hom. )

Consequence

SLAMF1
NM_003037.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

9 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:

ENSG00000228863 (HGNC:):

ENSG00000228863 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF1	NM_003037.5 link	c.-33C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000302035.11	NP_003028.1	Q13291-1
SLAMF1	NM_003037.5 link	c.-33C>T		5_prime_UTR_variant	Exon 1 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.-33C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_003037.5	ENSP00000306190.6		Q13291-1
SLAMF1	ENST00000302035.11 link	c.-33C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_003037.5	ENSP00000306190.6		Q13291-1

Frequencies

GnomAD3 genomes

AF:

0.0705

AC:

10720

AN:

152024

Hom.:

424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0540

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0696

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0560

AC:

12415

AN:

221768

AF XY:

0.0552

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.0228

Gnomad EAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.0594

Gnomad NFE exome

AF:

0.0720

Gnomad OTH exome

AF:

0.0610

GnomAD4 exome

AF:

0.0635

AC:

68309

AN:

1075030

Hom.:

2456

Cov.:

AF XY:

0.0623

AC XY:

34277

AN XY:

550210

show subpopulations

African (AFR)

AF:

0.105

AC:

2799

AN:

26732

American (AMR)

AF:

0.0410

AC:

1677

AN:

40942

Ashkenazi Jewish (ASJ)

AF:

0.0234

AC:

549

AN:

23500

East Asian (EAS)

AF:

0.00307

AC:

115

AN:

37440

South Asian (SAS)

AF:

0.0327

AC:

2522

AN:

77170

European-Finnish (FIN)

AF:

0.0614

AC:

3159

AN:

51476

Middle Eastern (MID)

AF:

0.0429

AC:

216

AN:

5032

European-Non Finnish (NFE)

AF:

0.0711

AC:

54397

AN:

765220

Other (OTH)

AF:

0.0605

AC:

2875

AN:

47518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

3131

6262

9394

12525

15656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1640

3280

4920

6560

8200

<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:

0.0706

AC:

10739

AN:

152142

Hom.:

427

Cov.:

AF XY:

0.0687

AC XY:

5112

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.103

AC:

4272

AN:

41492

American (AMR)

AF:

0.0483

AC:

738

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3472

East Asian (EAS)

AF:

0.00290

AC:

AN:

5164

South Asian (SAS)

AF:

0.0268

AC:

129

AN:

4822

European-Finnish (FIN)

AF:

0.0540

AC:

572

AN:

10588

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0696

AC:

4735

AN:

68000

Other (OTH)

AF:

0.0625

AC:

132

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

525

1050

1576

2101

2626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0647

Hom.:

Bravo

AF:

0.0723

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

0.31

PromoterAI

-0.14

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over