rs17801985

chr2-101842806-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001395002.1(MAP4K4):c.1022+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 612,446 control chromosomes in the GnomAD database, including 14,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2967 hom., cov: 32)
  • Exomes 𝑓: 0.20 (11379 hom.)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-101842806-A-G is Benign according to our data. Variant chr2-101842806-A-G is described in ClinVar as [Benign]. Clinvar id is 1240478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.1022+125A>G		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.1022+125A>G		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26150 AN: 152046 Hom.: 2967 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.201 AC: 92675 AN: 460282 Hom.: 11379 AF XY: 0.197 AC XY: 47495 AN XY: 240606

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.000980

Gnomad4 SAS exome AF: 0.0731

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.172 AC: 26154 AN: 152164 Hom.: 2967 Cov.: 32 AF XY: 0.173 AC XY: 12879 AN XY: 74376

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.164

Alfa AF: 0.224 Hom.: 866

Bravo AF: 0.150

Asia WGS AF: 0.0420 AC: 150 AN: 3478

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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.010
Dann	Benign	0.44

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: rs17801985; hg19: chr2-102459268;