Variant 4-38796804-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003263.4(TLR1):c.2028C>T(p.Gly676Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00728 in 1,614,188 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 58 hom. )

Consequence

TLR1
NM_003263.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.181

Variant links:

Genes affected

TLR1 (HGNC:11847): (toll like receptor 1) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. [provided by RefSeq, Jul 2008]

TLR1 links:

TLR1 (HGNC:):

TLR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 4-38796804-G-A is Benign according to our data. Variant chr4-38796804-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 786815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.181 with no splicing effect.

BS2

High AC in GnomAd4 at 879 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLR1	NM_003263.4 linkuse as main transcript	c.2028C>T	p.Gly676Gly	synonymous_variant	4/4	ENST00000308979.7	NP_003254.2	Q15399

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TLR1	ENST00000308979.7 linkuse as main transcript	c.2028C>T	p.Gly676Gly	synonymous_variant	4/4	1	NM_003263.4	ENSP00000354932.2	Q15399
TLR1	ENST00000502213.6 linkuse as main transcript	c.2028C>T	p.Gly676Gly	synonymous_variant	3/3	1		ENSP00000421259.1	Q15399
TLR1	ENST00000505744.5 linkuse as main transcript	n.235+4053C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

877

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00826

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00710

AC:

1784

AN:

251418

Hom.:

AF XY:

0.00737

AC XY:

1002

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00559

Gnomad FIN exome

AF:

0.00674

Gnomad NFE exome

AF:

0.00988

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.00744

AC:

10878

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

5503

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.00964

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00490

Gnomad4 FIN exome

AF:

0.00694

Gnomad4 NFE exome

AF:

0.00817

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.00577

AC:

879

AN:

152298

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00828

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00691

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00853

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	TLR1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.0

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over