rs11265452

Variant names:

• chr1-160624448-A-G
• rs11265452
• NM_003037.5:c.701-263T>C

Variant summary

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

The NM_003037.5(SLAMF1):​c.701-263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,080 control chromosomes in the GnomAD database, including 9,004 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 0.32 (9004 hom., cov: 31)
• Consequence: SLAMF1 NM_003037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 5 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 (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF1	NM_003037.5	c.701-263T>C		intron_variant	Intron 3 of 6	ENST00000302035.11	NP_003028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.701-263T>C		intron_variant	Intron 3 of 6	1	NM_003037.5	ENSP00000306190.6
SLAMF1	ENST00000538290.2	c.701-263T>C		intron_variant	Intron 3 of 7	1		ENSP00000438406.2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49171 AN: 151962 Hom.: 8985 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 49228 AN: 152080 Hom.: 9004 Cov.: 31 AF XY: 0.314 AC XY: 23348 AN XY: 74366

African (AFR) AF: 0.487 AC: 20173 AN: 41448

American (AMR) AF: 0.247 AC: 3778 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3468

East Asian (EAS) AF: 0.123 AC: 635 AN: 5180

South Asian (SAS) AF: 0.153 AC: 739 AN: 4824

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10584

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19677 AN: 67974

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.307 Hom.: 2118

Bravo AF: 0.336

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11265452; hg19: chr1-160594238; COSMIC: COSV107245179;