rs3796504

Variant names:

• chr1-160610759-G-T
• rs3796504
• NM_003037.5:c.997C>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.997C>A​(p.Pro333Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0803 in 1,611,012 control chromosomes in the GnomAD database, including 5,787 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 0.061 (380 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5407 hom.)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69
• Publications: 32 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018964708).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF1	NM_003037.5	MANE Select	c.997C>A	p.Pro333Thr	missense	Exon 7 of 7	NP_003028.1	Q13291-1
	SLAMF1	NM_001330754.2		c.*6C>A		3_prime_UTR	Exon 8 of 8	NP_001317683.1	Q13291-4
	SLAMF1	NR_104399.3		n.1022C>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF1	ENST00000302035.11	TSL:1 MANE Select	c.997C>A	p.Pro333Thr	missense	Exon 7 of 7	ENSP00000306190.6	Q13291-1
	SLAMF1	ENST00000878659.1		c.907C>A	p.Pro303Thr	missense	Exon 6 of 6	ENSP00000548717.1
	SLAMF1	ENST00000878657.1		c.658C>A	p.Pro220Thr	missense	Exon 6 of 6	ENSP00000548716.1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9363 AN: 152186 Hom.: 382 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0757

GnomAD2 exomes AF: 0.0699 AC: 17536 AN: 251018 AF XY: 0.0713

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.0430

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.000871

Gnomad FIN exome AF: 0.0675

Gnomad NFE exome AF: 0.0961

Gnomad OTH exome AF: 0.0818

GnomAD4 exome AF: 0.0822 AC: 119946 AN: 1458708 Hom.: 5407 Cov.: 29 AF XY: 0.0819 AC XY: 59451 AN XY: 725792

African (AFR) AF: 0.0112 AC: 374 AN: 33442

American (AMR) AF: 0.0452 AC: 2020 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3151 AN: 26088

East Asian (EAS) AF: 0.00774 AC: 307 AN: 39686

South Asian (SAS) AF: 0.0593 AC: 5109 AN: 86202

European-Finnish (FIN) AF: 0.0713 AC: 3809 AN: 53406

Middle Eastern (MID) AF: 0.0872 AC: 502 AN: 5758

European-Non Finnish (NFE) AF: 0.0901 AC: 99955 AN: 1109136

Other (OTH) AF: 0.0783 AC: 4719 AN: 60294

GnomAD4 genome AF: 0.0614 AC: 9355 AN: 152304 Hom.: 380 Cov.: 33 AF XY: 0.0607 AC XY: 4519 AN XY: 74470

African (AFR) AF: 0.0154 AC: 642 AN: 41586

American (AMR) AF: 0.0616 AC: 942 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3470

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5190

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4826

European-Finnish (FIN) AF: 0.0666 AC: 706 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0895 AC: 6089 AN: 68020

Other (OTH) AF: 0.0750 AC: 158 AN: 2108

Alfa AF: 0.0836 Hom.: 2759

Bravo AF: 0.0606

ESP6500AA AF: 0.0175 AC: 77

ESP6500EA AF: 0.0888 AC: 764

ExAC AF: 0.0719 AC: 8731

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.0927

EpiControl AF: 0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.16
MPC		0.84
ClinPred		0.029	T
GERP RS		4.1
Varity_R		0.25
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3796504; hg19: chr1-160580549; COSMIC: COSV52502577; COSMIC: COSV52502577;