Genetic Variant MAP4K1:c.533+145G>A (chr19-38613735-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001042600.3(MAP4K1):c.533+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 645,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MAP4K1
NM_001042600.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

8 publications found

Variant links:

Genes affected

MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAP4K1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042600.3. 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
	MAP4K1	NM_001042600.3	MANE Select	c.533+145G>A		intron	N/A	NP_001036065.1	Q92918-2
	MAP4K1	NM_007181.6		c.533+145G>A		intron	N/A	NP_009112.1	Q92918-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAP4K1	ENST00000396857.7	TSL:5 MANE Select	c.533+145G>A	intron	N/A	ENSP00000380066.1	Q92918-2
MAP4K1	ENST00000591517.5	TSL:1	c.533+145G>A	intron	N/A	ENSP00000465039.1	Q92918-1
MAP4K1	ENST00000864511.1		c.533+145G>A	intron	N/A	ENSP00000534570.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000286

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000243

AC:

AN:

494282

Hom.:

AF XY:

0.0000271

AC XY:

AN XY:

258572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13230

American (AMR)

AF:

0.00

AC:

AN:

19130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14134

East Asian (EAS)

AF:

0.00

AC:

AN:

31196

South Asian (SAS)

AF:

0.00

AC:

AN:

45476

European-Finnish (FIN)

AF:

0.000289

AC:

AN:

31164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2052

European-Non Finnish (NFE)

AF:

0.00000644

AC:

AN:

310362

Other (OTH)

AF:

0.0000363

AC:

AN:

27538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151252

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73772

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41076

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.000286

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67858

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

1985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

(source)

DANN

Benign

0.96

PhyloP100

-0.0090

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over