chr1-160612458-C-G

Position:

• chr1-160612458-C-G

Variant summary

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

The NM_003037.5(SLAMF1):​c.957+30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,445,430 control chromosomes in the GnomAD database, including 146,030 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 0.37 (12140 hom., cov: 29)
  • Exomes 𝑓: 0.45 (133890 hom.)
• Consequence: SLAMF1 NM_003037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.957+30G>C		intron_variant		ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.957+30G>C		intron_variant		1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.1040+30G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55468 AN: 151638 Hom.: 12133 Cov.: 29

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.353

GnomAD3 exomes AF: 0.451 AC: 105249 AN: 233262 Hom.: 25017 AF XY: 0.460 AC XY: 57707 AN XY: 125522

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.683

Gnomad SAS exome AF: 0.515

Gnomad FIN exome AF: 0.523

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.449 AC: 580548 AN: 1293674 Hom.: 133890 Cov.: 17 AF XY: 0.452 AC XY: 294063 AN XY: 650840

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.366 AC: 55496 AN: 151756 Hom.: 12140 Cov.: 29 AF XY: 0.374 AC XY: 27734 AN XY: 74108

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.358

Alfa AF: 0.403 Hom.: 2494

Bravo AF: 0.341

Asia WGS AF: 0.533 AC: 1853 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.62

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: rs11265449; hg19: chr1-160582248; COSMIC: COSV52497486;