rs16886397

chr5-56838449-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005921.2(MAP3K1):c.483-18151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,328 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (286 hom., cov: 32)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

Genes affected

MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-56838449-A-G is Benign according to our data. Variant chr5-56838449-A-G is described in ClinVar as [Benign]. Clinvar id is 539066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K1	NM_005921.2	c.483-18151A>G		intron_variant		ENST00000399503.4
MAP3K1	XM_047417218.1	c.483-18151A>G		intron_variant
MAP3K1	XM_047417219.1	c.71+17633A>G		intron_variant
MAP3K1	XM_047417220.1	c.71+17633A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4	c.483-18151A>G		intron_variant		1	NM_005921.2	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9020 AN: 152210 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0592 AC: 9021 AN: 152328 Hom.: 286 Cov.: 32 AF XY: 0.0596 AC XY: 4440 AN XY: 74488

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0633 Hom.: 77

Bravo AF: 0.0589

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

46,XY sex reversal 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	14
Dann	Benign	0.90

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: rs16886397; hg19: chr5-56134276;