rs2025515

chr1-160612423-C-Achr1-160612423-C-Gchr1-160612423-C-T

Variant summary

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

The NM_003037.5(SLAMF1):c.957+65G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,006,452 control chromosomes in the GnomAD database, including 67,852 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 0.36 (11844 hom., cov: 28)
  • Exomes 𝑓: 0.41 (56008 hom.)
• Consequence: SLAMF1 NM_003037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.957+65G>T		intron_variant		ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.957+65G>T		intron_variant		1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.1040+65G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 54857 AN: 150690 Hom.: 11841 Cov.: 28

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.411 AC: 351735 AN: 855656 Hom.: 56008 AF XY: 0.412 AC XY: 179924 AN XY: 436532

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.394

GnomAD4 genome AF: 0.364 AC: 54877 AN: 150796 Hom.: 11844 Cov.: 28 AF XY: 0.372 AC XY: 27390 AN XY: 73582

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.354

Alfa AF: 0.236 Hom.: 1209

Bravo AF: 0.341

Asia WGS AF: 0.517 AC: 1797 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.13
Dann	Benign	0.24

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: rs2025515; hg19: chr1-160582213;