1-160635073-A-T

Variant summary

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

The NM_003037.5(SLAMF1):c.416-176T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,058 control chromosomes in the GnomAD database, including 32,073 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 0.65 (32073 hom., cov: 31)
• Consequence: SLAMF1 NM_003037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF1	NM_003037.5	c.416-176T>A		intron_variant		ENST00000302035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF1	ENST00000302035.11	c.416-176T>A		intron_variant		1	NM_003037.5	P1
SLAMF1	ENST00000538290.2	c.416-176T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98275 AN: 151940 Hom.: 32029 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.647 AC: 98377 AN: 152058 Hom.: 32073 Cov.: 31 AF XY: 0.650 AC XY: 48317 AN XY: 74338

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.632

Alfa AF: 0.651 Hom.: 4032

Bravo AF: 0.639

Asia WGS AF: 0.648 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.7
Dann	Benign	0.72

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: rs3766362; hg19: chr1-160604863;