Variant 4-6036057-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099433.2(JAKMIP1):c.2226G>A(p.Pro742=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,557,330 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 6 hom. )

Consequence

JAKMIP1
NM_001099433.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.85

Variant links:

Genes affected

JAKMIP1 (HGNC:26460): (janus kinase and microtubule interacting protein 1) Enables GABA receptor binding activity and RNA binding activity. Involved in cognition. Is extrinsic component of membrane. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

JAKMIP1 links:

C4orf50 (HGNC:33766): (chromosome 4 open reading frame 50)

C4orf50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-6036057-C-T is Benign according to our data. Variant chr4-6036057-C-T is described in ClinVar as [Benign]. Clinvar id is 714239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0051 (777/152388) while in subpopulation AFR AF= 0.0166 (691/41604). AF 95% confidence interval is 0.0156. There are 4 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAKMIP1	NM_001099433.2 linkuse as main transcript	c.2226G>A	p.Pro742=	synonymous_variant	19/21	ENST00000409021.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAKMIP1	ENST00000409021.9 linkuse as main transcript	c.2226G>A	p.Pro742=	synonymous_variant	19/21	1	NM_001099433.2	P1	Q96N16-2
JAKMIP1	ENST00000409371.8 linkuse as main transcript	c.1671G>A	p.Pro557=	synonymous_variant	17/19	1			Q96N16-5
JAKMIP1	ENST00000637373.2 linkuse as main transcript	c.930G>A	p.Pro310=	synonymous_variant	12/14	5
C4orf50	ENST00000531445.3 linkuse as main transcript	c.-2721G>A		5_prime_UTR_variant	19/34	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00508

AC:

774

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00138

AC:

224

AN:

162812

Hom.:

AF XY:

0.00121

AC XY:

105

AN XY:

86786

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000989

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000432

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.0000769

Gnomad OTH exome

AF:

0.000440

GnomAD4 exome

AF:

0.000590

AC:

829

AN:

1404942

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

391

AN XY:

693548

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000880

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.0000249

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00510

AC:

777

AN:

152388

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

351

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00593

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.94

DANN

Benign

0.59

Splicing

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