2-101697929-C-CCCG

Position:

• chr2-101697929-C-CCCG

Variant summary

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

The NM_001395002.1(MAP4K4):​c.-140_-138dup 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 0.28 (6482 hom., cov: 15)
  • Exomes 𝑓: 0.23 (1419 hom.)
• Consequence: MAP4K4 NM_001395002.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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 2-101697929-C-CCCG is Benign according to our data. Variant chr2-101697929-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 1238946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.-140_-138dup		5_prime_UTR_variant	1/33	ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.-140_-138dup		5_prime_UTR_variant	1/33	5	NM_001395002.1	P3
MAP4K4	ENST00000350878.9	c.-140_-138dup		5_prime_UTR_variant	1/31	1
MAP4K4	ENST00000427603.5	c.-5-135_-5-133dup		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 40908 AN: 144976 Hom.: 6481 Cov.: 15

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.227 AC: 11488 AN: 50658 Hom.: 1419 Cov.: 4 AF XY: 0.226 AC XY: 5924 AN XY: 26238

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.282 AC: 40895 AN: 145068 Hom.: 6482 Cov.: 15 AF XY: 0.285 AC XY: 20096 AN XY: 70502

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.296

Alfa AF: 0.0983 Hom.: 133

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 20, 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: rs577276891; hg19: chr2-102314391;