Variant 1-160612502-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003037.5(SLAMF1):c.943C>T(p.Pro315Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,609,868 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 62 hom. )

Consequence

SLAMF1
NM_003037.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027861297).

BP6

Variant 1-160612502-G-A is Benign according to our data. Variant chr1-160612502-G-A is described in ClinVar as [Benign]. Clinvar id is 717815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2002/152100) while in subpopulation AFR AF= 0.0454 (1883/41474). AF 95% confidence interval is 0.0437. There are 45 homozygotes in gnomad4. There are 982 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF1	NM_003037.5 link	c.943C>T	p.Pro315Ser	missense_variant	6/7	ENST00000302035.11	NP_003028.1	Q13291-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11 link	c.943C>T	p.Pro315Ser	missense_variant	6/7	1	NM_003037.5	ENSP00000306190.6		Q13291-1
SLAMF1	ENST00000538290.2 link	c.1026C>T	p.Ser342Ser	synonymous_variant	7/8	1		ENSP00000438406.2		Q13291-4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2001

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.00329

AC:

820

AN:

249572

Hom.:

AF XY:

0.00230

AC XY:

310

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00141

AC:

2060

AN:

1457768

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

879

AN XY:

725334

show subpopulations

Gnomad4 AFR exome

AF:

0.0501

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000649

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.0132

AC:

2002

AN:

152100

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

982

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.00576

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.0149

ESP6500AA

AF:

0.0440

AC:

194

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00398

AC:

483

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.0056

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.16

MVP

0.80

MPC

0.75

ClinPred

0.065

GERP RS

3.4

Varity_R

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over