6-90540522-C-T

Variant names:

• chr6-90540522-C-T
• rs157692
• NM_145331.3:c.1291+4030G>A

Variant summary

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

The NM_145331.3(MAP3K7):​c.1291+4030G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,738 control chromosomes in the GnomAD database, including 33,081 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 0.66 (33081 hom., cov: 33)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.1291+4030G>A		intron_variant	Intron 12 of 16	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.1291+4030G>A		intron_variant	Intron 12 of 16	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99703 AN: 151620 Hom.: 33066 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.657 AC: 99760 AN: 151738 Hom.: 33081 Cov.: 33 AF XY: 0.652 AC XY: 48369 AN XY: 74130

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.693

Alfa AF: 0.664 Hom.: 3976

Bravo AF: 0.652

Asia WGS AF: 0.570 AC: 1977 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.48

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: rs157692; hg19: chr6-91250241;