rs8110231

chr19-35905132-C-T

Variant summary

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

The NM_003332.4(TYROBP):c.277-498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,230 control chromosomes in the GnomAD database, including 961 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 0.072 (961 hom., cov: 31)
• Consequence: TYROBP NM_003332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

TYROBP (HGNC:12449): (transmembrane immune signaling adaptor TYROBP) This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Multiple alternative transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYROBP	NM_003332.4	c.277-498G>A		intron_variant		ENST00000262629.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYROBP	ENST00000262629.9	c.277-498G>A		intron_variant		1	NM_003332.4	P4

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10934 AN: 152112 Hom.: 938 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0723 AC: 11000 AN: 152230 Hom.: 961 Cov.: 31 AF XY: 0.0696 AC XY: 5180 AN XY: 74436

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0403 Hom.: 107

Bravo AF: 0.0814

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.40
Dann	Benign	0.64

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: rs8110231; hg19: chr19-36396034;