17-45264774-G-C

Position:

• chr17-45264774-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003954.5(MAP3K14):​c.2706C>G​(p.Val902=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 0.0730

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

ACMG classification

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/exons	MANE	Protein	UniProt
MAP3K14	NM_003954.5	c.2706C>G	p.Val902=	synonymous_variant	16/16	ENST00000344686.8	NP_003945.2
MAP3K14-AS1	NR_110325.1	n.260-2339G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K14	ENST00000344686.8	c.2706C>G	p.Val902=	synonymous_variant	16/16	1	NM_003954.5	ENSP00000478552	P1
MAP3K14-AS1	ENST00000657572.1	n.170-2339G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112402 AN: 152002 Hom.: 41747 Cov.: 32

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

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.: 62 AF XY: 0.720 AC XY: 522990 AN XY: 726414

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.: 32 AF XY: 0.736 AC XY: 54742 AN XY: 74356

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:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other: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 01, 2024

- -

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

Other links and lift over

dbSNP: rs1047833; hg19: chr17-43342141;