rs572189095

Variant names:

• chr2-101698171-GGGCAGCC-G
• rs572189095
• NM_001395002.1:c.57+51_57+57delCAGCCGG

Your query was ambiguous. Multiple possible variants found:

• chr2-101698171-GGGCAGCC-G
• chr2-101698171-GGGCAGCC-GGGCAGCCGGCAGCC
• chr2-101698171-GGGCAGCC-GGGCAGCCGGCAGCCGGCAGCC
• chr2-101698171-GGGCAGCC-GGGCAGCCGGCAGCCGGCAGCCGGCAGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001395002.1(MAP4K4):​c.57+51_57+57delCAGCCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000605 in 959,404 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000077 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4K4	NM_001395002.1	c.57+51_57+57delCAGCCGG		intron_variant	Intron 1 of 32	ENST00000324219.9	NP_001381931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4K4	ENST00000324219.9	c.57+35_57+41delGGCAGCC		intron_variant	Intron 1 of 32	5	NM_001395002.1	ENSP00000313644.6

Frequencies

GnomAD3 genomes AF: 0.0000766 AC: 11 AN: 143522 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000919

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000501 AC: 6 AN: 119656 Hom.: 0 AF XY: 0.0000430 AC XY: 3 AN XY: 69752

Gnomad AFR exome AF: 0.000239

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000175

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000606

Gnomad NFE exome AF: 0.0000506

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000576 AC: 47 AN: 815774 Hom.: 0 AF XY: 0.0000529 AC XY: 21 AN XY: 396906

Gnomad4 AFR exome AF: 0.000173

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000109

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000604

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000551

Gnomad4 OTH exome AF: 0.0000726

GnomAD4 genome AF: 0.0000766 AC: 11 AN: 143630 Hom.: 0 Cov.: 22 AF XY: 0.000115 AC XY: 8 AN XY: 69868

Gnomad4 AFR AF: 0.0000512

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000627

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000919

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000147 Hom.: 346

ClinVar

Not reported in ClinVar

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;