rs13430871

Variant names:

• chr2-101697473-C-T
• rs13430871
• ENST00000933920.1:c.-608C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000933920.1(MAP4K4):​c.-608C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 151,558 control chromosomes in the GnomAD database, including 2,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.098 (2072 hom., cov: 31)
• Consequence: MAP4K4 ENST00000933920.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.340
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 2-101697473-C-T is Benign according to our data. Variant chr2-101697473-C-T is described in ClinVar as Benign. ClinVar VariationId is 1240597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000933920.1. 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.-608C>T		upstream_gene	N/A	NP_001381931.1	G5E948
	MAP4K4	NM_001384497.1		c.-608C>T		upstream_gene	N/A	NP_001371426.1
	MAP4K4	NM_001384492.1		c.-608C>T		upstream_gene	N/A	NP_001371421.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4K4	ENST00000933920.1		c.-608C>T		5_prime_UTR	Exon 1 of 29	ENSP00000603979.1
	MAP4K4	ENST00000933918.1		c.-6+201C>T		intron	N/A	ENSP00000603977.1
	MAP4K4	ENST00000427603.5	TSL:4	c.-6+409C>T		intron	N/A	ENSP00000403016.1	E7ETN6

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14847 AN: 151450 Hom.: 2066 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.000286

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.0824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0982 AC: 14880 AN: 151558 Hom.: 2072 Cov.: 31 AF XY: 0.0952 AC XY: 7051 AN XY: 74068

African (AFR) AF: 0.315 AC: 13001 AN: 41328

American (AMR) AF: 0.0646 AC: 986 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4818

European-Finnish (FIN) AF: 0.000286 AC: 3 AN: 10500

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00963 AC: 653 AN: 67824

Other (OTH) AF: 0.0815 AC: 171 AN: 2098

Alfa AF: 0.0357 Hom.: 405

Bravo AF: 0.114

Asia WGS AF: 0.0190 AC: 67 AN: 3458

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
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		0.34
PromoterAI		0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs13430871; hg19: chr2-102313935;