Variant chr17-45264774-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003954.5(MAP3K14):c.2706C>G(p.Val902Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,612,602 control chromosomes in the GnomAD database, including 423,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41771 hom., cov: 32)

Exomes 𝑓: 0.72 ( 381710 hom. )

Consequence

MAP3K14
NM_003954.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.0730

Variant links:

Genes affected

MAP3K14 (HGNC:6853): (mitogen-activated protein kinase kinase kinase 14) This gene encodes mitogen-activated protein kinase kinase kinase 14, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-kappaB activity. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. [provided by RefSeq, Jul 2008]

MAP3K14 links:

MAP3K14-AS1 (HGNC:44359): (MAP3K14 antisense RNA 1)

MAP3K14-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-45264774-G-C is Benign according to our data. Variant chr17-45264774-G-C is described in ClinVar as [Benign]. Clinvar id is 1170667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K14	NM_003954.5 link	c.2706C>G	p.Val902Val	synonymous_variant	Exon 16 of 16	ENST00000344686.8	NP_003945.2	Q99558Q68D39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8 link	c.2706C>G	p.Val902Val	synonymous_variant	Exon 16 of 16	1	NM_003954.5	ENSP00000478552.1		Q99558

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112402

AN:

152002

Hom.:

41747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.695

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.716

GnomAD3 exomes

AF:

0.716

AC:

176317

AN:

246148

Hom.:

63303

AF XY:

0.711

AC XY:

95106

AN XY:

133686

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.682

Gnomad EAS exome

AF:

0.732

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.698

Gnomad NFE exome

AF:

0.720

Gnomad OTH exome

AF:

0.695

GnomAD4 exome

AF:

0.722

AC:

1055113

AN:

1460482

Hom.:

381710

Cov.:

AF XY:

0.720

AC XY:

522990

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.754

Gnomad4 ASJ exome

AF:

0.684

Gnomad4 EAS exome

AF:

0.771

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.705

Gnomad4 NFE exome

AF:

0.725

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.739

AC:

112470

AN:

152120

Hom.:

41771

Cov.:

AF XY:

0.736

AC XY:

54742

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.758

Gnomad4 ASJ

AF:

0.695

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.702

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.714

Alfa

AF:

0.729

Hom.:

13096

Bravo

AF:

0.744

Asia WGS

AF:

0.696

AC:

2420

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

NIK deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.4

DANN

Benign

0.61

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