chr22-50601349-C-A

Position:

• chr22-50601349-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000329492.6(MAPK8IP2):​c.66-440C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 171,542 control chromosomes in the GnomAD database, including 10,693 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 0.32 (9209 hom., cov: 32)
  • Exomes 𝑓: 0.37 (1484 hom.)
• Consequence: MAPK8IP2 ENST00000329492.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

Genes affected

MAPK8IP2 (HGNC:6883): (mitogen-activated protein kinase 8 interacting protein 2) This gene encodes a scaffold protein that is thought to be involved in the regulation of the c-Jun amino-terminal kinase signaling pathway. This protein has been shown to interact with and regulate the activity of MAPK8/JNK1 and MAP2K7/MKK7 kinases. [provided by RefSeq, Jun 2017]

CHKB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK8IP2	NM_012324.6	c.66-440C>A		intron_variant		ENST00000329492.6	NP_036456.1
MAPK8IP2	XM_011530679.3	c.66-440C>A		intron_variant			XP_011528981.1
MAPK8IP2	XM_011530680.3	c.66-440C>A		intron_variant			XP_011528982.1
MAPK8IP2	XM_011530681.3	c.66-440C>A		intron_variant			XP_011528983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK8IP2	ENST00000329492.6	c.66-440C>A		intron_variant		1	NM_012324.6	ENSP00000330572.4
CHKB	ENST00000463053.1	n.107G>T		non_coding_transcript_exon_variant	1/7	3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48644 AN: 151948 Hom.: 9213 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.372 AC: 7250 AN: 19476 Hom.: 1484 Cov.: 0 AF XY: 0.366 AC XY: 3796 AN XY: 10378

Gnomad4 AFR exome AF: 0.0876

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.320 AC: 48644 AN: 152066 Hom.: 9209 Cov.: 32 AF XY: 0.324 AC XY: 24093 AN XY: 74344

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.323

Alfa AF: 0.399 Hom.: 18129

Bravo AF: 0.303

Asia WGS AF: 0.301 AC: 1047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.5
DANN	Benign	0.84

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: rs2238834; hg19: chr22-51039778;