rs462572

Variant names:

• chr6-90530454-C-G
• rs462572
• NM_145331.3:c.1356+5883G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-90530454-C-G
• chr6-90530454-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145331.3(MAP3K7):​c.1356+5883G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,660 control chromosomes in the GnomAD database, including 10,476 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 0.36 (10476 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 2 publications found

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]

MAP3K7 Gene-Disease associations (from GenCC):

• cardiospondylocarpofacial syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• frontometaphyseal dysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina
• frontometaphyseal dysplasia 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.1356+5883G>C		intron_variant	Intron 13 of 16	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.1356+5883G>C		intron_variant	Intron 13 of 16	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55207 AN: 151540 Hom.: 10462 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.365 AC: 55281 AN: 151660 Hom.: 10476 Cov.: 32 AF XY: 0.360 AC XY: 26657 AN XY: 74130

African (AFR) AF: 0.477 AC: 19719 AN: 41298

American (AMR) AF: 0.346 AC: 5282 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1618 AN: 3460

East Asian (EAS) AF: 0.315 AC: 1624 AN: 5162

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2508 AN: 10552

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21250 AN: 67802

Other (OTH) AF: 0.390 AC: 822 AN: 2108

Alfa AF: 0.325 Hom.: 1000

Bravo AF: 0.375

Asia WGS AF: 0.359 AC: 1249 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs462572; hg19: chr6-91240173; COSMIC: COSV65223924;