chr6-41228995-C-T

Variant names:

• chr6-41228995-C-T
• rs147088240
• NM_198153.3:c.345C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_198153.3(TREML4):​c.345C>T​(p.Ser115Ser) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.895
• Publications: 2 publications found

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]

ENSG00000290563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML4	NM_198153.3	MANE Select	c.345C>T	p.Ser115Ser	synonymous	Exon 2 of 6	NP_937796.1	Q6UXN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREML4	ENST00000341495.7	TSL:1 MANE Select	c.345C>T	p.Ser115Ser	synonymous	Exon 2 of 6	ENSP00000342570.2	Q6UXN2
	TREML4	ENST00000448827.6	TSL:1	c.345C>T	p.Ser115Ser	synonymous	Exon 2 of 6	ENSP00000418078.1	Q6UXN2
	ENSG00000290563	ENST00000564680.6	TSL:1	n.206-11001G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 479 AN: 152176 Hom.: 1 Cov.: 31

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

GnomAD2 exomes AF: 0.00314 AC: 788 AN: 251352 AF XY: 0.00319

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 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.: 13 Cov.: 36 AF XY: 0.00379 AC XY: 2754 AN XY: 727206

African (AFR) AF: 0.000657 AC: 22 AN: 33478

American (AMR) AF: 0.00452 AC: 202 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00582 AC: 152 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86250

European-Finnish (FIN) AF: 0.00116 AC: 62 AN: 53418

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.00439 AC: 4878 AN: 1111926

Other (OTH) AF: 0.00409 AC: 247 AN: 60392

GnomAD4 genome AF: 0.00315 AC: 479 AN: 152294 Hom.: 1 Cov.: 31 AF XY: 0.00303 AC XY: 226 AN XY: 74466

African (AFR) AF: 0.00128 AC: 53 AN: 41546

American (AMR) AF: 0.00693 AC: 106 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00398 AC: 271 AN: 68020

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00449 Hom.: 1

Bravo AF: 0.00394

EpiCase AF: 0.00523

EpiControl AF: 0.00486

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.58
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147088240; hg19: chr6-41196733; COSMIC: COSV58385368;