rs12076998

Positions:

• chr1-160646978-G-A

Variant summary

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

The NM_003037.5(SLAMF1):​c.-33C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,227,172 control chromosomes in the GnomAD database, including 2,883 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 0.071 (427 hom., cov: 31)
  • Exomes 𝑓: 0.064 (2456 hom.)
• Consequence: SLAMF1 NM_003037.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

LOC107985220 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF1	NM_003037.5	c.-33C>T		5_prime_UTR_variant	1/7	ENST00000302035.11	NP_003028.1
LOC107985220	XR_001738266.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.-33C>T		5_prime_UTR_variant	1/7	1	NM_003037.5	ENSP00000306190	P1
SLAMF1	ENST00000494463.1	n.44C>T		non_coding_transcript_exon_variant	1/2	1
SLAMF1	ENST00000538290.2			upstream_gene_variant		1		ENSP00000438406

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10720 AN: 152024 Hom.: 424 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0632

GnomAD3 exomes AF: 0.0560 AC: 12415 AN: 221768 Hom.: 429 AF XY: 0.0552 AC XY: 6609 AN XY: 119706

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0400

Gnomad ASJ exome AF: 0.0228

Gnomad EAS exome AF: 0.00392

Gnomad SAS exome AF: 0.0320

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.0720

Gnomad OTH exome AF: 0.0610

GnomAD4 exome AF: 0.0635 AC: 68309 AN: 1075030 Hom.: 2456 Cov.: 14 AF XY: 0.0623 AC XY: 34277 AN XY: 550210

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0410

Gnomad4 ASJ exome AF: 0.0234

Gnomad4 EAS exome AF: 0.00307

Gnomad4 SAS exome AF: 0.0327

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0711

Gnomad4 OTH exome AF: 0.0605

GnomAD4 genome AF: 0.0706 AC: 10739 AN: 152142 Hom.: 427 Cov.: 31 AF XY: 0.0687 AC XY: 5112 AN XY: 74372

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0268

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0647 Hom.: 79

Bravo AF: 0.0723

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.60

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: rs12076998; hg19: chr1-160616768; COSMIC: COSV52503122; COSMIC: COSV52503122;