19-38613735-C-T

Variant names:

• chr19-38613735-C-T
• rs750438
• NM_001042600.3:c.533+145G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 8 publications found

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

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4K1	NM_001042600.3	c.533+145G>A		intron_variant	Intron 8 of 30	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6	c.533+145G>A		intron_variant	Intron 8 of 31		NP_009112.1
MAP4K1	XM_011526404.2	c.533+145G>A		intron_variant	Intron 8 of 31		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7	c.533+145G>A		intron_variant	Intron 8 of 30	5	NM_001042600.3	ENSP00000380066.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151252 Hom.: 0 Cov.: 29

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: 12 AN: 494282 Hom.: 0 AF XY: 0.0000271 AC XY: 7 AN XY: 258572

African (AFR) AF: 0.00 AC: 0 AN: 13230

American (AMR) AF: 0.00 AC: 0 AN: 19130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14134

East Asian (EAS) AF: 0.00 AC: 0 AN: 31196

South Asian (SAS) AF: 0.00 AC: 0 AN: 45476

European-Finnish (FIN) AF: 0.000289 AC: 9 AN: 31164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2052

European-Non Finnish (NFE) AF: 0.00000644 AC: 2 AN: 310362

Other (OTH) AF: 0.0000363 AC: 1 AN: 27538

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151252 Hom.: 0 Cov.: 29 AF XY: 0.0000407 AC XY: 3 AN XY: 73772

African (AFR) AF: 0.0000243 AC: 1 AN: 41076

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.000286 AC: 3 AN: 10476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 1985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
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

Other links and lift over

dbSNP: rs750438; hg19: chr19-39104375;