Variant 6-41228995-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_198153.3(TREML4):c.345C>T(p.Ser115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,614,076 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0039 ( 13 hom. )

Consequence

TREML4
NM_198153.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.895

Variant links:

Genes affected

TREML4 (HGNC:30807): (triggering receptor expressed on myeloid cells like 4) Predicted to enable signaling receptor activity. Involved in positive regulation of toll-like receptor 7 signaling pathway. Predicted to be located in endoplasmic reticulum. Predicted to be active in cell surface. Predicted to colocalize with endosome membrane and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

TREML4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-41228995-C-T is Benign according to our data. Variant chr6-41228995-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656542.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.895 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREML4	NM_198153.3 linkuse as main transcript	c.345C>T	p.Ser115=	synonymous_variant	2/6	ENST00000341495.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TREML4	ENST00000341495.7 linkuse as main transcript	c.345C>T	p.Ser115=	synonymous_variant	2/6	1	NM_198153.3	P1
TREML4	ENST00000448827.6 linkuse as main transcript	c.345C>T	p.Ser115=	synonymous_variant	2/6	1		P1
TREML4	ENST00000461240.1 linkuse as main transcript	c.42C>T	p.Ser14=	synonymous_variant, NMD_transcript_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

479

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00314

AC:

788

AN:

251352

Hom.:

AF XY:

0.00319

AC XY:

433

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00385

AC:

5631

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

2754

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.00582

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000475

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00439

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00315

AC:

479

AN:

152294

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

226

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00449

Hom.:

Bravo

AF:

0.00394

EpiCase

AF:

0.00523

EpiControl

AF:

0.00486

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

TREML4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.9

DANN

Benign

0.58

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

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