chr2-101698171-G-GGGCAGCC

Position:

• chr2-101698171-G-GGGCAGCC

Variant summary

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

The NM_001395002.1(MAP4K4):​c.57+51_57+57dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 958,432 control chromosomes in the GnomAD database, including 26,326 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4807 hom., cov: 22)
  • Exomes 𝑓: 0.18 (21519 hom.)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225

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 2-101698171-G-GGGCAGCC is Benign according to our data. Variant chr2-101698171-G-GGGCAGCC is described in ClinVar as [Benign]. Clinvar id is 1231613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.57+51_57+57dup		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.57+51_57+57dup		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 34916 AN: 143464 Hom.: 4806 Cov.: 22

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.250

GnomAD3 exomes AF: 0.0509 AC: 6093 AN: 119656 Hom.: 1250 AF XY: 0.0456 AC XY: 3180 AN XY: 69752

Gnomad AFR exome AF: 0.00286

Gnomad AMR exome AF: 0.00698

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.000706

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0361

GnomAD4 exome AF: 0.182 AC: 148042 AN: 814862 Hom.: 21519 Cov.: 13 AF XY: 0.179 AC XY: 71121 AN XY: 396418

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.0427

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0860

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.243 AC: 34929 AN: 143570 Hom.: 4807 Cov.: 22 AF XY: 0.249 AC XY: 17385 AN XY: 69832

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.247

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs572189095; hg19: chr2-102314633;