9-125460745-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPKAP1	NM_001006617.3	c.1345+7227T>C		intron_variant		ENST00000265960.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.1345+7227T>C		intron_variant		1	NM_001006617.3	P1

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

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.486

Alfa AF: 0.420 Hom.: 6479

Bravo AF: 0.505

Asia WGS AF: 0.381 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.1
Dann	Benign	0.62

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: rs7853181; hg19: chr9-128223024;