2-101697975-T-C

Position:

• chr2-101697975-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001395002.1(MAP4K4):​c.-106T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 694,944 control chromosomes in the GnomAD database, including 173,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42272 hom., cov: 33)
  • Exomes 𝑓: 0.69 (130872 hom.)
• Consequence: MAP4K4 NM_001395002.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.27

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-101697975-T-C is Benign according to our data. Variant chr2-101697975-T-C is described in ClinVar as [Benign]. Clinvar id is 1259880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K4	NM_001395002.1	c.-106T>C		5_prime_UTR_variant	1/33	ENST00000324219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K4	ENST00000324219.9	c.-106T>C		5_prime_UTR_variant	1/33	5	NM_001395002.1	P3
MAP4K4	ENST00000350878.9	c.-106T>C		5_prime_UTR_variant	1/31	1
MAP4K4	ENST00000427603.5	c.-5-101T>C		intron_variant		4
MAP4K4	ENST00000425019.6			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.755 AC: 110693 AN: 146664 Hom.: 42224 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.687 AC: 376805 AN: 548186 Hom.: 130872 Cov.: 8 AF XY: 0.688 AC XY: 191972 AN XY: 278996

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.688

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.755 AC: 110785 AN: 146758 Hom.: 42272 Cov.: 33 AF XY: 0.757 AC XY: 54092 AN XY: 71410

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.728

Alfa AF: 0.690 Hom.: 15996

Bravo AF: 0.760

Asia WGS AF: 0.743 AC: 1689 AN: 2272

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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13430711; hg19: chr2-102314437;