Variant 19-38587707-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001042600.3(MAP4K1):c.*41C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,439,774 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 22 hom. )

Consequence

MAP4K1
NM_001042600.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.185

Variant links:

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]

MAP4K1 links:

RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

RYR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-38587707-G-C is Benign according to our data. Variant chr19-38587707-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1223674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
MAP4K1	NM_001042600.3 linkuse as main transcript	c.*41C>G	3_prime_UTR_variant	31/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6 linkuse as main transcript	c.*103C>G	3_prime_UTR_variant	32/32		NP_009112.1
MAP4K1	XM_011526404.2 linkuse as main transcript	c.*41C>G	3_prime_UTR_variant	32/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7 linkuse as main transcript	c.*41C>G		3_prime_UTR_variant	31/31	5	NM_001042600.3	ENSP00000380066	P1	Q92918-2

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00247

AC:

613

AN:

248062

Hom.:

AF XY:

0.00311

AC XY:

418

AN XY:

134558

show subpopulations

Gnomad AFR exome

AF:

0.00227

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00168

AC:

2167

AN:

1287468

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

1375

AN XY:

649826

show subpopulations

Gnomad4 AFR exome

AF:

0.00378

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000779

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152306

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.00145

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.0

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over