chr17-12141985-T-TG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003010.4(MAP2K4):​c.*728dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 233,360 control chromosomes in the GnomAD database, including 59 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 36 hom., cov: 32)
Exomes 𝑓: 0.021 ( 23 hom. )

Consequence

MAP2K4
NM_003010.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54
Variant links:
Genes affected
MAP2K4 (HGNC:6844): (mitogen-activated protein kinase kinase 4) This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP2K4NM_003010.4 linkuse as main transcriptc.*728dup 3_prime_UTR_variant 11/11 ENST00000353533.10
MAP2K4NM_001281435.2 linkuse as main transcriptc.*728dup 3_prime_UTR_variant 12/12
MAP2K4XM_005256753.4 linkuse as main transcriptc.*728dup 3_prime_UTR_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP2K4ENST00000353533.10 linkuse as main transcriptc.*728dup 3_prime_UTR_variant 11/111 NM_003010.4 P2P45985-1
MAP2K4ENST00000415385.7 linkuse as main transcriptc.*728dup 3_prime_UTR_variant 12/122 A2P45985-2
MAP2K4ENST00000536413.2 linkuse as main transcriptn.2110dup non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.0205
AC:
3125
AN:
152162
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0271
Gnomad AMI
AF:
0.0768
Gnomad AMR
AF:
0.0125
Gnomad ASJ
AF:
0.00864
Gnomad EAS
AF:
0.0595
Gnomad SAS
AF:
0.00414
Gnomad FIN
AF:
0.0253
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0159
Gnomad OTH
AF:
0.0167
GnomAD4 exome
AF:
0.0212
AC:
1716
AN:
81080
Hom.:
23
Cov.:
0
AF XY:
0.0202
AC XY:
754
AN XY:
37314
show subpopulations
Gnomad4 AFR exome
AF:
0.0261
Gnomad4 AMR exome
AF:
0.0108
Gnomad4 ASJ exome
AF:
0.00785
Gnomad4 EAS exome
AF:
0.0617
Gnomad4 SAS exome
AF:
0.00143
Gnomad4 FIN exome
AF:
0.0216
Gnomad4 NFE exome
AF:
0.0144
Gnomad4 OTH exome
AF:
0.0171
GnomAD4 genome
AF:
0.0206
AC:
3132
AN:
152280
Hom.:
36
Cov.:
32
AF XY:
0.0209
AC XY:
1556
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0272
Gnomad4 AMR
AF:
0.0125
Gnomad4 ASJ
AF:
0.00864
Gnomad4 EAS
AF:
0.0596
Gnomad4 SAS
AF:
0.00393
Gnomad4 FIN
AF:
0.0253
Gnomad4 NFE
AF:
0.0159
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.0153
Hom.:
4
Bravo
AF:
0.0219
Asia WGS
AF:
0.0220
AC:
77
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28921114; hg19: chr17-12045302; API