rs17718580

Positions:

• chr14-50506914-C-T

Variant summary

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

The NM_006575.6(MAP4K5):​c.109-2057G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,208 control chromosomes in the GnomAD database, including 503 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 0.072 (503 hom., cov: 32)
• Consequence: MAP4K5 NM_006575.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940

Genes affected

MAP4K5 (HGNC:6867): (mitogen-activated protein kinase kinase kinase kinase 5) This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K5	NM_006575.6	c.109-2057G>A		intron_variant		ENST00000682126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K5	ENST00000682126.1	c.109-2057G>A		intron_variant			NM_006575.6	P1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10929 AN: 152090 Hom.: 503 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0718 AC: 10923 AN: 152208 Hom.: 503 Cov.: 32 AF XY: 0.0712 AC XY: 5300 AN XY: 74434

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0972

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0876 Hom.: 376

Bravo AF: 0.0675

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.80

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: rs17718580; hg19: chr14-50973632;