chr2-101697929-C-CCCG

Variant names:

• chr2-101697929-C-CCCG
• rs577276891
• NM_001395002.1:c.-140_-138dupGCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001395002.1(MAP4K4):​c.-140_-138dupGCC 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
• Publications: 1 publications found

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]

MAP4K4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395002.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K4	NM_001395002.1	MANE Select	c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 33	NP_001381931.1	G5E948
	MAP4K4	NM_001384497.1		c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 32	NP_001371426.1
	MAP4K4	NM_001384492.1		c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 33	NP_001371421.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K4	ENST00000324219.9	TSL:5 MANE Select	c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 33	ENSP00000313644.6	G5E948
	MAP4K4	ENST00000350878.9	TSL:1	c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 31	ENSP00000343658.5	O95819-6
	MAP4K4	ENST00000902131.1		c.-140_-138dupGCC		5_prime_UTR	Exon 1 of 31	ENSP00000572190.1

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

African (AFR) AF: 0.0749 AC: 49 AN: 654

American (AMR) AF: 0.116 AC: 22 AN: 190

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 71 AN: 294

East Asian (EAS) AF: 0.356 AC: 136 AN: 382

South Asian (SAS) AF: 0.394 AC: 529 AN: 1342

European-Finnish (FIN) AF: 0.271 AC: 3578 AN: 13226

Middle Eastern (MID) AF: 0.179 AC: 40 AN: 224

European-Non Finnish (NFE) AF: 0.205 AC: 6783 AN: 33014

Other (OTH) AF: 0.210 AC: 280 AN: 1332

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

African (AFR) AF: 0.148 AC: 6027 AN: 40630

American (AMR) AF: 0.284 AC: 4171 AN: 14706

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1323 AN: 3374

East Asian (EAS) AF: 0.494 AC: 2347 AN: 4752

South Asian (SAS) AF: 0.492 AC: 2340 AN: 4754

European-Finnish (FIN) AF: 0.275 AC: 2286 AN: 8298

Middle Eastern (MID) AF: 0.299 AC: 83 AN: 278

European-Non Finnish (NFE) AF: 0.327 AC: 21375 AN: 65370

Other (OTH) AF: 0.296 AC: 595 AN: 2008

Alfa AF: 0.0983 Hom.: 133

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs577276891; hg19: chr2-102314391;