rs1017226

Positions:

• chr5-56857565-T-C
• chr5-56857565-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005921.2(MAP3K1):​c.633+815T>C 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 152,264 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (284 hom., cov: 32)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.804

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-56857565-T-C is Benign according to our data. Variant chr5-56857565-T-C is described in ClinVar as [Benign]. Clinvar id is 1598785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K1	NM_005921.2	c.633+815T>C		intron_variant		ENST00000399503.4
MAP3K1	XM_047417218.1	c.633+815T>C		intron_variant
MAP3K1	XM_047417219.1	c.222+815T>C		intron_variant
MAP3K1	XM_047417220.1	c.222+815T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K1	ENST00000399503.4	c.633+815T>C		intron_variant		1	NM_005921.2	P1
	ENST00000415589.1	n.336+2104A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9010 AN: 152146 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0662

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: 9011 AN: 152264 Hom.: 284 Cov.: 32 AF XY: 0.0595 AC XY: 4429 AN XY: 74452

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0537 Hom.: 83

Bravo AF: 0.0589

Asia WGS AF: 0.0740 AC: 257 AN: 3476

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	-0.92
CADD	Benign	0.49
DANN	Benign	0.39

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: rs1017226; hg19: chr5-56153392;