2-135045855-G-T

Variant names:

• chr2-135045855-G-T
• rs4954218
• NM_025052.5:c.-424+1330C>A

Variant summary

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

The NM_025052.5(MAP3K19):​c.-424+1330C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,246 control chromosomes in the GnomAD database, including 53,987 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 0.83 (53987 hom., cov: 33)
• Consequence: MAP3K19 NM_025052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 39 publications found

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025052.5. 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
	MAP3K19	NM_025052.5	MANE Select	c.-424+1330C>A		intron	N/A	NP_079328.3	Q56UN5-1
	MAP3K19	NM_001400438.1		c.-480+1330C>A		intron	N/A	NP_001387367.1	Q56UN5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K19	ENST00000392915.7	TSL:5 MANE Select	c.-424+1330C>A		intron	N/A	ENSP00000376647.2	Q56UN5-1
	MAP3K19	ENST00000468155.5	TSL:1	n.284+1330C>A		intron	N/A
	MAP3K19	ENST00000637841.1	TSL:5	c.-288+1330C>A		intron	N/A	ENSP00000489676.1	A0A1B0GTF4

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126795 AN: 152128 Hom.: 53925 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.834 AC: 126915 AN: 152246 Hom.: 53987 Cov.: 33 AF XY: 0.841 AC XY: 62591 AN XY: 74446

African (AFR) AF: 0.950 AC: 39454 AN: 41544

American (AMR) AF: 0.889 AC: 13601 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3262 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5182 AN: 5190

South Asian (SAS) AF: 0.859 AC: 4139 AN: 4820

European-Finnish (FIN) AF: 0.815 AC: 8635 AN: 10596

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49913 AN: 68000

Other (OTH) AF: 0.868 AC: 1835 AN: 2114

Alfa AF: 0.772 Hom.: 193723

Bravo AF: 0.846

Asia WGS AF: 0.952 AC: 3310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.58
DANN	Benign	0.37
PhyloP100		-0.084

Splicing

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

Other links and lift over

dbSNP: rs4954218; hg19: chr2-135803425;