Variant 22-50077379-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.525+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,602,054 control chromosomes in the GnomAD database, including 17,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1735 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15998 hom. )

Consequence

MLC1
NM_015166.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.03

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:

MLC1 (HGNC:):

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=-0.92).

BP6

Variant 22-50077379-C-T is Benign according to our data. Variant chr22-50077379-C-T is described in ClinVar as [Benign]. Clinvar id is 260574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4 linkuse as main transcript	c.525+22G>A		intron_variant		ENST00000311597.10	NP_055981.1	Q15049-1A0A024R4V4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MLC1	ENST00000311597.10 linkuse as main transcript	c.525+22G>A	intron_variant	1	NM_015166.4	ENSP00000310375.6	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.525+22G>A	intron_variant	1		ENSP00000379216.2	Q15049-1
MLC1	ENST00000442311.1 linkuse as main transcript	c.435+22G>A	intron_variant	5		ENSP00000401385.1	A6PVC3

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21757

AN:

152114

Hom.:

1719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.167

AC:

41386

AN:

247908

Hom.:

3890

AF XY:

0.163

AC XY:

21912

AN XY:

134462

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.203

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.145

AC:

209850

AN:

1449822

Hom.:

15998

Cov.:

AF XY:

0.145

AC XY:

104432

AN XY:

721788

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.143

AC:

21793

AN:

152232

Hom.:

1735

Cov.:

AF XY:

0.143

AC XY:

10672

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.150

Hom.:

339

Bravo

AF:

0.151

Asia WGS

AF:

0.183

AC:

635

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Megalencephalic leukoencephalopathy with subcortical cysts 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.17

DANN

Benign

0.69

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