rs1197790

Variant names:

• chr11-64795886-G-A
• rs1197790
• NM_004579.5:c.1751+387C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004579.5(MAP4K2):​c.1751+387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 150,954 control chromosomes in the GnomAD database, including 18 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 0.0086 (18 hom., cov: 32)
• Consequence: MAP4K2 NM_004579.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 0 publications found

Genes affected

MAP4K2 (HGNC:6864): (mitogen-activated protein kinase kinase kinase kinase 2) The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00865 (1305/150954) while in subpopulation AFR AF = 0.029 (1171/40418). AF 95% confidence interval is 0.0276. There are 18 homozygotes in GnomAd4. There are 602 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4K2	NM_004579.5	c.1751+387C>T		intron_variant	Intron 24 of 31	ENST00000294066.7	NP_004570.2
MAP4K2	NM_001307990.2	c.1727+387C>T		intron_variant	Intron 24 of 31		NP_001294919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4K2	ENST00000294066.7	c.1751+387C>T		intron_variant	Intron 24 of 31	1	NM_004579.5	ENSP00000294066.2

Frequencies

GnomAD3 genomes AF: 0.00864 AC: 1303 AN: 150842 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00773

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

GnomAD4 genome AF: 0.00865 AC: 1305 AN: 150954 Hom.: 18 Cov.: 32 AF XY: 0.00816 AC XY: 602 AN XY: 73804

African (AFR) AF: 0.0290 AC: 1171 AN: 40418

American (AMR) AF: 0.00210 AC: 32 AN: 15246

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

East Asian (EAS) AF: 0.0134 AC: 69 AN: 5166

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67930

Other (OTH) AF: 0.00813 AC: 17 AN: 2092

Alfa AF: 0.00569 Hom.: 1

Bravo AF: 0.00941

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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: rs1197790; hg19: chr11-64563358;