NM_001395002.1:c.1234-5118T>C

Variant names:

• chr2-101850859-T-C
• rs972372
• NM_001395002.1:c.1234-5118T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395002.1(MAP4K4):​c.1234-5118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,120 control chromosomes in the GnomAD database, including 35,628 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (35628 hom., cov: 33)
• Consequence: MAP4K4 NM_001395002.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4K4	NM_001395002.1	c.1234-5118T>C		intron_variant	Intron 12 of 32	ENST00000324219.9	NP_001381931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4K4	ENST00000324219.9	c.1234-5118T>C		intron_variant	Intron 12 of 32	5	NM_001395002.1	ENSP00000313644.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102522 AN: 152002 Hom.: 35570 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.675 AC: 102645 AN: 152120 Hom.: 35628 Cov.: 33 AF XY: 0.676 AC XY: 50252 AN XY: 74386

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.643

Alfa AF: 0.616 Hom.: 38102

Bravo AF: 0.681

Asia WGS AF: 0.550 AC: 1914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
DANN	Benign	0.70

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: rs972372; hg19: chr2-102467321; COSMIC: COSV56328144;