Variant chr22-50059747-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015166.4(MLC1):c.*1836G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,446 control chromosomes in the GnomAD database, including 871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 871 hom., cov: 33)

Exomes 𝑓: 0.074 ( 0 hom. )

Consequence

MLC1
NM_015166.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.83

Variant links:

Genes affected

MLC1 (HGNC:17082): (modulator of VRAC current 1) The function of this gene product is unknown; however, homology to other proteins suggests that it may be an integral membrane transporter. Mutations in this gene have been associated with megalencephalic leukoencephalopathy with subcortical cysts, an autosomal recessive neurological disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MLC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 22-50059747-C-T is Benign according to our data. Variant chr22-50059747-C-T is described in ClinVar as [Benign]. Clinvar id is 342076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLC1	NM_015166.4 linkuse as main transcript	c.*1836G>A		3_prime_UTR_variant	12/12	ENST00000311597.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLC1	ENST00000311597.10 linkuse as main transcript	c.*1836G>A		3_prime_UTR_variant	12/12	1	NM_015166.4	P1	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.*1836G>A		3_prime_UTR_variant	12/12	1		P1	Q15049-1

Frequencies

GnomAD3 genomes

AF:

0.0974

AC:

14811

AN:

152124

Hom.:

871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0534

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0814

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.0563

Gnomad FIN

AF:

0.0977

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.0735

AC:

AN:

204

Hom.:

Cov.:

AF XY:

0.0809

AC XY:

AN XY:

136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.0700

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.0973

AC:

14808

AN:

152242

Hom.:

871

Cov.:

AF XY:

0.0947

AC XY:

7049

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0532

Gnomad4 AMR

AF:

0.0813

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.0194

Gnomad4 SAS

AF:

0.0561

Gnomad4 FIN

AF:

0.0977

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.121

Hom.:

314

Bravo

AF:

0.0942

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

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

-1.0

CADD

Benign

0.12

DANN

Benign

0.62

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