rs7752459

Variant names:

• chr6-36116895-C-T
• rs7752459
• ENST00000718318.1:c.*403C>T

Variant summary

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

The ENST00000718318.1(MAPK14):​c.*403C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,156 control chromosomes in the GnomAD database, including 1,234 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 0.12 (1234 hom., cov: 32)
• Consequence: MAPK14 ENST00000718318.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 8 publications found

Genes affected

MAPK14 (HGNC:6876): (mitogen-activated protein kinase 14) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases 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. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

BRPF3-AS1 (HGNC:55591): (BRPF3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK14	XM_047418234.1	c.*403C>T		3_prime_UTR_variant	Exon 11 of 11		XP_047274190.1
MAPK14	XM_047418233.1	c.1027+474C>T		intron_variant	Intron 11 of 11		XP_047274189.1
MAPK14	XM_047418235.1	c.1027+474C>T		intron_variant	Intron 11 of 11		XP_047274191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK14	ENST00000718318.1	c.*403C>T		3_prime_UTR_variant	Exon 11 of 11			ENSP00000520752.1
MAPK14	ENST00000718319.1	c.904+474C>T		intron_variant	Intron 11 of 11			ENSP00000520753.1
BRPF3-AS1	ENST00000816533.1	n.398-3561G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18403 AN: 152036 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.121 AC: 18418 AN: 152156 Hom.: 1234 Cov.: 32 AF XY: 0.119 AC XY: 8889 AN XY: 74390

African (AFR) AF: 0.186 AC: 7696 AN: 41472

American (AMR) AF: 0.0755 AC: 1155 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3466

East Asian (EAS) AF: 0.105 AC: 541 AN: 5176

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4820

European-Finnish (FIN) AF: 0.0844 AC: 894 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6794 AN: 68010

Other (OTH) AF: 0.108 AC: 228 AN: 2114

Alfa AF: 0.111 Hom.: 386

Bravo AF: 0.124

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7752459; hg19: chr6-36084672;