6-90518704-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_145331.3(MAP3K7):c.1525-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 595,778 control chromosomes in the GnomAD database, including 19,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4640 hom., cov: 32)
  • Exomes 𝑓: 0.25 (15005 hom.)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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=-0.3).
• BP6: Variant 6-90518704-A-G is Benign according to our data. Variant chr6-90518704-A-G is described in ClinVar as [Benign]. Clinvar id is 1276654.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7	NM_145331.3	c.1525-142T>C		intron_variant		ENST00000369329.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7	ENST00000369329.8	c.1525-142T>C		intron_variant		1	NM_145331.3	P3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36326 AN: 151608 Hom.: 4642 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.248 AC: 109967 AN: 444052 Hom.: 15005 AF XY: 0.242 AC XY: 58191 AN XY: 240450

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.0873

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.239 AC: 36319 AN: 151726 Hom.: 4640 Cov.: 32 AF XY: 0.238 AC XY: 17649 AN XY: 74168

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.236

Alfa AF: 0.270 Hom.: 716

Bravo AF: 0.227

Asia WGS AF: 0.157 AC: 544 AN: 3474

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	17
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: rs1145727; hg19: chr6-91228423; COSMIC: COSV65226351;