1-160646913-G-T

Variant names:

• chr1-160646913-G-T
• rs2295612
• NM_003037.5:c.33C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003037.5(SLAMF1):​c.33C>A​(p.Phe11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,599,616 control chromosomes in the GnomAD database, including 29,962 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2115 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27847 hom.)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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]

ENSG00000228863 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009170055).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF1	NM_003037.5	c.33C>A	p.Phe11Leu	missense_variant	Exon 1 of 7	ENST00000302035.11	NP_003028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.33C>A	p.Phe11Leu	missense_variant	Exon 1 of 7	1	NM_003037.5	ENSP00000306190.6
SLAMF1	ENST00000538290.2	c.33C>A	p.Phe11Leu	missense_variant	Exon 1 of 8	1		ENSP00000438406.2
SLAMF1	ENST00000494463.1	n.109C>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000228863	ENST00000840728.1	n.-121G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22076 AN: 152016 Hom.: 2113 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.169 AC: 41871 AN: 248184 AF XY: 0.167

Gnomad AFR exome AF: 0.0314

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.0428

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.189 AC: 273000 AN: 1447482 Hom.: 27847 Cov.: 27 AF XY: 0.187 AC XY: 134482 AN XY: 720724

African (AFR) AF: 0.0309 AC: 1030 AN: 33374

American (AMR) AF: 0.270 AC: 11947 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3797 AN: 25994

East Asian (EAS) AF: 0.0504 AC: 1995 AN: 39596

South Asian (SAS) AF: 0.119 AC: 10215 AN: 85858

European-Finnish (FIN) AF: 0.149 AC: 7922 AN: 53140

Middle Eastern (MID) AF: 0.144 AC: 828 AN: 5742

European-Non Finnish (NFE) AF: 0.205 AC: 225039 AN: 1099682

Other (OTH) AF: 0.171 AC: 10227 AN: 59852

GnomAD4 genome AF: 0.145 AC: 22077 AN: 152134 Hom.: 2115 Cov.: 32 AF XY: 0.143 AC XY: 10626 AN XY: 74372

African (AFR) AF: 0.0397 AC: 1649 AN: 41536

American (AMR) AF: 0.224 AC: 3426 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3472

East Asian (EAS) AF: 0.0422 AC: 218 AN: 5162

South Asian (SAS) AF: 0.101 AC: 486 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1486 AN: 10566

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13725 AN: 67976

Other (OTH) AF: 0.155 AC: 327 AN: 2112

Alfa AF: 0.182 Hom.: 12429

Bravo AF: 0.149

TwinsUK AF: 0.210 AC: 778

ALSPAC AF: 0.212 AC: 816

ESP6500AA AF: 0.0359 AC: 158

ESP6500EA AF: 0.203 AC: 1748

ExAC AF: 0.162 AC: 19703

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.97
DANN	Benign	0.55
DEOGEN2	Benign	0.042	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.54	T;T;T
MetaRNN	Benign	0.0092	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.12	N;.;N
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.36	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.67	T;T;T
Sift4G	Benign	0.78	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.0070
MutPred		0.46		Gain of disorder (P = 0.163);Gain of disorder (P = 0.163);Gain of disorder (P = 0.163);
MPC		0.24
ClinPred		0.00044	T
GERP RS		0.79
PromoterAI		-0.25	Neutral
Varity_R		0.033
gMVP		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs2295612; hg19: chr1-160616703; COSMIC: COSV52498809;