rs205348

Variant names:

• chr6-90545651-G-A
• rs205348
• NM_145331.3:c.1211-1019C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-90545651-G-A
• chr6-90545651-G-C

Variant summary

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

The NM_145331.3(MAP3K7):​c.1211-1019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,984 control chromosomes in the GnomAD database, including 9,114 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 0.34 (9114 hom., cov: 32)
• Consequence: MAP3K7 NM_145331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP3K7	NM_145331.3	c.1211-1019C>T		intron_variant	Intron 11 of 16	ENST00000369329.8	NP_663304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP3K7	ENST00000369329.8	c.1211-1019C>T		intron_variant	Intron 11 of 16	1	NM_145331.3	ENSP00000358335.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52031 AN: 151866 Hom.: 9104 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.343 AC: 52086 AN: 151984 Hom.: 9114 Cov.: 32 AF XY: 0.339 AC XY: 25166 AN XY: 74292

African (AFR) AF: 0.402 AC: 16646 AN: 41436

American (AMR) AF: 0.337 AC: 5138 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1612 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1630 AN: 5148

South Asian (SAS) AF: 0.423 AC: 2036 AN: 4816

European-Finnish (FIN) AF: 0.238 AC: 2519 AN: 10564

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

European-Non Finnish (NFE) AF: 0.314 AC: 21337 AN: 67974

Other (OTH) AF: 0.370 AC: 781 AN: 2112

Alfa AF: 0.326 Hom.: 1050

Bravo AF: 0.348

Asia WGS AF: 0.354 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		-0.18
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: rs205348; hg19: chr6-91255370; COSMIC: COSV65223953;