rs3817624

chr19-35907997-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003332.4(TYROBP):c.61+171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,084 control chromosomes in the GnomAD database, including 595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.083 (595 hom., cov: 31)
• Consequence: TYROBP NM_003332.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.648

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-35907997-C-T is Benign according to our data. Variant chr19-35907997-C-T is described in ClinVar as [Benign]. Clinvar id is 1288066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYROBP	NM_003332.4	c.61+171G>A		intron_variant		ENST00000262629.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYROBP	ENST00000262629.9	c.61+171G>A		intron_variant		1	NM_003332.4	P4

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12578 AN: 151966 Hom.: 594 Cov.: 31

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0827 AC: 12583 AN: 152084 Hom.: 595 Cov.: 31 AF XY: 0.0843 AC XY: 6266 AN XY: 74332

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.0978

Gnomad4 OTH AF: 0.0830

Alfa AF: 0.0926 Hom.: 918

Bravo AF: 0.0829

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.44

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: rs3817624; hg19: chr19-36398899;