rs750438

chr19-38613735-C-Achr19-38613735-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042600.3(MAP4K1):c.533+145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 645,220 control chromosomes in the GnomAD database, including 17,812 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 0.24 (5487 hom., cov: 29)
  • Exomes 𝑓: 0.20 (12325 hom.)
• Consequence: MAP4K1 NM_001042600.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4K1	NM_001042600.3	c.533+145G>T		intron_variant		ENST00000396857.7
MAP4K1	NM_007181.6	c.533+145G>T		intron_variant
MAP4K1	XM_011526404.2	c.533+145G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4K1	ENST00000396857.7	c.533+145G>T		intron_variant		5	NM_001042600.3	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36748 AN: 151160 Hom.: 5452 Cov.: 29

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.201 AC: 99153 AN: 493942 Hom.: 12325 AF XY: 0.206 AC XY: 53290 AN XY: 258372

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.244 AC: 36848 AN: 151278 Hom.: 5487 Cov.: 29 AF XY: 0.250 AC XY: 18496 AN XY: 73844

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.241

Alfa AF: 0.155 Hom.: 1113

Bravo AF: 0.262

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.4
Dann	Benign	0.72

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: rs750438; hg19: chr19-39104375;