rs1145728

Positions:

• chr6-90544033-A-T

Variant summary

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

The NM_145331.3(MAP3K7):​c.1291+519T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,960 control chromosomes in the GnomAD database, including 3,988 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 0.21 (3988 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

MAP3K7 (HGNC:6859): (mitogen-activated protein kinase kinase kinase 7) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7	NM_145331.3	c.1291+519T>A		intron_variant		ENST00000369329.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7	ENST00000369329.8	c.1291+519T>A		intron_variant		1	NM_145331.3	P3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31822 AN: 151842 Hom.: 3990 Cov.: 32

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.209 AC: 31816 AN: 151960 Hom.: 3988 Cov.: 32 AF XY: 0.209 AC XY: 15492 AN XY: 74236

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0977

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.218

Alfa AF: 0.253 Hom.: 676

Bravo AF: 0.193

Asia WGS AF: 0.152 AC: 527 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.82

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: rs1145728; hg19: chr6-91253752; COSMIC: COSV65225869;