1-160612502-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 46 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.943C>T	p.Pro315Ser	missense_variant	6/7	1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.1026C>T	p.Ser342=	synonymous_variant	7/8	1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2001 AN: 151982 Hom.: 46 Cov.: 31

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.: 20 AF XY: 0.00230 AC XY: 310 AN XY: 134816

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.: 62 Cov.: 29 AF XY: 0.00121 AC XY: 879 AN XY: 725334

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.: 45 Cov.: 31 AF XY: 0.0132 AC XY: 982 AN XY: 74368

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.: 56

Bravo AF: 0.0149

ESP6500AA AF: 0.0440 AC: 194

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00398 AC: 483

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.0056
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.16
MVP		0.80
MPC		0.75
ClinPred		0.065	T
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

Other links and lift over

dbSNP: rs35207844; hg19: chr1-160582292;