2-101697716-A-ACT

Position:

• chr2-101697716-A-ACT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001395002.1(MAP4K4):​c.-363_-362dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (41493 hom., cov: 0)
  • Exomes 𝑓: 0.67 (197 hom.)
• Consequence: MAP4K4 NM_001395002.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.529

Genes affected

MAP4K4 (HGNC:6866): (mitogen-activated protein kinase kinase kinase kinase 4) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-101697716-A-ACT is Benign according to our data. Variant chr2-101697716-A-ACT is described in ClinVar as [Benign]. Clinvar id is 1225314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.-363_-362dup		5_prime_UTR_variant	1/33	ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.-363_-362dup		5_prime_UTR_variant	1/33	5	NM_001395002.1	P3
MAP4K4	ENST00000427603.5	c.-5-358_-5-357dup		intron_variant		4
MAP4K4	ENST00000350878.9			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 108914 AN: 144460 Hom.: 41446 Cov.: 0

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.667 AC: 574 AN: 860 Hom.: 197 Cov.: 0 AF XY: 0.650 AC XY: 277 AN XY: 426

Gnomad4 SAS exome AF: 0.668

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.754 AC: 109003 AN: 144546 Hom.: 41493 Cov.: 0 AF XY: 0.757 AC XY: 53204 AN XY: 70310

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.732

Alfa AF: 0.654 Hom.: 3188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200434935; hg19: chr2-102314178;