rs2548663

Positions:

• chr5-56876951-G-A
• chr5-56876951-G-C

Variant summary

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

The NM_005921.2(MAP3K1):​c.1965+1641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,982 control chromosomes in the GnomAD database, including 33,330 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 0.65 (33330 hom., cov: 31)
• Consequence: MAP3K1 NM_005921.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K1	NM_005921.2	c.1965+1641G>A		intron_variant		ENST00000399503.4	NP_005912.1
MAP3K1	XM_047417218.1	c.1965+1641G>A		intron_variant			XP_047273174.1
MAP3K1	XM_047417219.1	c.1554+1641G>A		intron_variant			XP_047273175.1
MAP3K1	XM_047417220.1	c.1554+1641G>A		intron_variant			XP_047273176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K1	ENST00000399503.4	c.1965+1641G>A		intron_variant		1	NM_005921.2	ENSP00000382423.3

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99213 AN: 151866 Hom.: 33301 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.653 AC: 99281 AN: 151982 Hom.: 33330 Cov.: 31 AF XY: 0.644 AC XY: 47826 AN XY: 74302

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.656

Alfa AF: 0.693 Hom.: 9041

Bravo AF: 0.638

Asia WGS AF: 0.387 AC: 1348 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.91

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: rs2548663; hg19: chr5-56172778;