rs164288

chr1-160634683-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003037.5(SLAMF1):c.630C>T(p.Thr210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 1,613,984 control chromosomes in the GnomAD database, including 5,754 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 0.065 (389 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5365 hom.)
• Consequence: SLAMF1 NM_003037.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-3.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.630C>T	p.Thr210=	synonymous_variant	3/7	ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.630C>T	p.Thr210=	synonymous_variant	3/7	1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.630C>T	p.Thr210=	synonymous_variant	3/8	1

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9949 AN: 152044 Hom.: 388 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0738

GnomAD3 exomes AF: 0.0725 AC: 18217 AN: 251284 Hom.: 850 AF XY: 0.0743 AC XY: 10092 AN XY: 135786

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.0447

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.00663

Gnomad SAS exome AF: 0.0657

Gnomad FIN exome AF: 0.0662

Gnomad NFE exome AF: 0.0946

Gnomad OTH exome AF: 0.0849

GnomAD4 exome AF: 0.0827 AC: 120894 AN: 1461822 Hom.: 5365 Cov.: 32 AF XY: 0.0825 AC XY: 60031 AN XY: 727214

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.0468

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.0697

Gnomad4 NFE exome AF: 0.0885

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0654 AC: 9954 AN: 152162 Hom.: 389 Cov.: 32 AF XY: 0.0638 AC XY: 4745 AN XY: 74380

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0597

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.0731

Alfa AF: 0.0864 Hom.: 789

Bravo AF: 0.0651

Asia WGS AF: 0.0400 AC: 140 AN: 3478

EpiCase AF: 0.0934

EpiControl AF: 0.0931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.34
Dann	Benign	0.63

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: rs164288; hg19: chr1-160604473; COSMIC: COSV52500994; COSMIC: COSV52500994;