chr2-135045855-G-T

Position:

• chr2-135045855-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K19	NM_025052.5	c.-424+1330C>A		intron_variant		ENST00000392915.7
MAP3K19	NM_001400438.1	c.-480+1330C>A		intron_variant
MAP3K19	XM_017005004.3	c.-392+1330C>A		intron_variant
MAP3K19	XM_017005005.3	c.-203+1330C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K19	ENST00000392915.7	c.-424+1330C>A		intron_variant		5	NM_025052.5	P2

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

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.868

Alfa AF: 0.769 Hom.: 98872

Bravo AF: 0.846

Asia WGS AF: 0.952 AC: 3310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4954218; hg19: chr2-135803425;