rs1503854

Positions:

• chr1-160629220-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000302035.11(SLAMF1):​c.701-5035T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,984 control chromosomes in the GnomAD database, including 8,139 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 0.32 (8139 hom., cov: 31)
• Consequence: SLAMF1 ENST00000302035.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF1	NM_003037.5	c.701-5035T>C		intron_variant		ENST00000302035.11	NP_003028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.701-5035T>C		intron_variant		1	NM_003037.5	ENSP00000306190	P1
SLAMF1	ENST00000538290.2	c.701-5035T>C		intron_variant		1		ENSP00000438406

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48588 AN: 151868 Hom.: 8128 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48620 AN: 151984 Hom.: 8139 Cov.: 31 AF XY: 0.311 AC XY: 23116 AN XY: 74276

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.348

Alfa AF: 0.373 Hom.: 14030

Bravo AF: 0.322

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.54

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: rs1503854; hg19: chr1-160599010; COSMIC: COSV52502452;