2-101698174-CA-C

Position:

• chr2-101698174-CA-C

Variant summary

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

The NM_001395002.1(MAP4K4):​c.57+38del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 920,490 control chromosomes in the GnomAD database, including 1,195 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (808 hom., cov: 31)
  • Exomes 𝑓: 0.015 (387 hom.)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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 2-101698174-CA-C is Benign according to our data. Variant chr2-101698174-CA-C is described in ClinVar as [Benign]. Clinvar id is 1221787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.57+38del		intron_variant		ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.57+38del		intron_variant		5	NM_001395002.1	P3

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9465 AN: 146412 Hom.: 809 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0199

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.00442

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000238

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.0519

GnomAD3 exomes AF: 0.0402 AC: 1561 AN: 38874 Hom.: 80 AF XY: 0.0339 AC XY: 769 AN XY: 22662

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00485

Gnomad FIN exome AF: 0.000497

Gnomad NFE exome AF: 0.0317

Gnomad OTH exome AF: 0.0539

GnomAD4 exome AF: 0.0150 AC: 11639 AN: 773972 Hom.: 387 Cov.: 12 AF XY: 0.0149 AC XY: 5480 AN XY: 368882

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.00928

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00440

Gnomad4 FIN exome AF: 0.000456

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.0202

GnomAD4 genome AF: 0.0647 AC: 9481 AN: 146518 Hom.: 808 Cov.: 31 AF XY: 0.0625 AC XY: 4461 AN XY: 71328

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.00442

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.000238

Gnomad4 NFE AF: 0.00927

Gnomad4 OTH AF: 0.0514

Alfa AF: 0.00312 Hom.: 5

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

- -

Computational scores

Source: dbNSFP v4.3

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: rs375488010; hg19: chr2-102314636;