14-70745441-A-G

Variant names:

• chr14-70745441-A-G
• rs10483834
• NM_001284230.2:c.1327-2850T>C

Variant summary

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

The NM_001284230.2(MAP3K9):​c.1327-2850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,066 control chromosomes in the GnomAD database, including 4,224 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 0.23 (4224 hom., cov: 32)
• Consequence: MAP3K9 NM_001284230.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 9 publications found

Genes affected

MAP3K9 (HGNC:6861): (mitogen-activated protein kinase kinase kinase 9) Enables protein serine/threonine kinase activity. Involved in protein autophosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284230.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K9	NM_001284230.2	MANE Select	c.1327-2850T>C		intron	N/A	NP_001271159.1
	MAP3K9	NM_033141.4		c.1327-2850T>C		intron	N/A	NP_149132.2
	MAP3K9	NM_001284231.1		c.538-2850T>C		intron	N/A	NP_001271160.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K9	ENST00000554752.7	TSL:1 MANE Select	c.1327-2850T>C		intron	N/A	ENSP00000451612.2
	MAP3K9	ENST00000555993.6	TSL:1	c.1327-2850T>C		intron	N/A	ENSP00000451263.2
	MAP3K9	ENST00000553414.5	TSL:1	c.409-2850T>C		intron	N/A	ENSP00000451038.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34491 AN: 151948 Hom.: 4219 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.227 AC: 34512 AN: 152066 Hom.: 4224 Cov.: 32 AF XY: 0.225 AC XY: 16730 AN XY: 74332

African (AFR) AF: 0.232 AC: 9638 AN: 41470

American (AMR) AF: 0.197 AC: 3005 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5166

South Asian (SAS) AF: 0.383 AC: 1850 AN: 4826

European-Finnish (FIN) AF: 0.192 AC: 2034 AN: 10586

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16033 AN: 67960

Other (OTH) AF: 0.231 AC: 486 AN: 2108

Alfa AF: 0.237 Hom.: 14276

Bravo AF: 0.218

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.80
PhyloP100		0.072
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: rs10483834; hg19: chr14-71212158;