9-125460745-A-G

Variant names:

• chr9-125460745-A-G
• rs7853181
• NM_001006617.3:c.1345+7227T>C

Variant summary

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

The NM_001006617.3(MAPKAP1):​c.1345+7227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,088 control chromosomes in the GnomAD database, including 19,433 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 0.50 (19433 hom., cov: 33)
• Consequence: MAPKAP1 NM_001006617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 7 publications found

Genes affected

MAPKAP1 (HGNC:18752): (MAPK associated protein 1) This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively spliced transcript variants encoding distinct isoforms have been described. Alternate polyadenylation sites as well as alternate 3' UTRs have been identified for transcripts of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	NM_001006617.3	MANE Select	c.1345+7227T>C		intron	N/A	NP_001006618.1
	MAPKAP1	NM_024117.4		c.1237+7227T>C		intron	N/A	NP_077022.1
	MAPKAP1	NM_001006619.2		c.1204+7227T>C		intron	N/A	NP_001006620.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	ENST00000265960.8	TSL:1 MANE Select	c.1345+7227T>C		intron	N/A	ENSP00000265960.3
	MAPKAP1	ENST00000350766.7	TSL:1	c.1237+7227T>C		intron	N/A	ENSP00000265961.5
	MAPKAP1	ENST00000373511.6	TSL:1	c.1204+7227T>C		intron	N/A	ENSP00000362610.2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75231 AN: 151970 Hom.: 19403 Cov.: 33

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.495 AC: 75305 AN: 152088 Hom.: 19433 Cov.: 33 AF XY: 0.492 AC XY: 36617 AN XY: 74358

African (AFR) AF: 0.646 AC: 26795 AN: 41470

American (AMR) AF: 0.467 AC: 7135 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1690 AN: 5172

South Asian (SAS) AF: 0.362 AC: 1749 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5027 AN: 10582

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29726 AN: 67982

Other (OTH) AF: 0.486 AC: 1026 AN: 2112

Alfa AF: 0.424 Hom.: 7398

Bravo AF: 0.505

Asia WGS AF: 0.381 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.070
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: rs7853181; hg19: chr9-128223024;