Variant 22-50074188-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.714+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,576,360 control chromosomes in the GnomAD database, including 151,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11766 hom., cov: 32)

Exomes 𝑓: 0.44 ( 139732 hom. )

Consequence

MLC1
NM_015166.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 22-50074188-C-T is Benign according to our data. Variant chr22-50074188-C-T is described in ClinVar as [Benign]. Clinvar id is 262458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 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.714+28G>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.714+28G>A	intron_variant	1	NM_015166.4	ENSP00000310375.6	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.714+28G>A	intron_variant	1		ENSP00000379216.2	Q15049-1
MLC1	ENST00000442311.1 linkuse as main transcript	c.624+28G>A	intron_variant	5		ENSP00000401385.1	A6PVC3
MLC1	ENST00000470008.1 linkuse as main transcript	n.194+28G>A	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57185

AN:

151874

Hom.:

11752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.405

AC:

94078

AN:

232462

Hom.:

19810

AF XY:

0.404

AC XY:

50917

AN XY:

126088

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.438

AC:

623499

AN:

1424368

Hom.:

139732

Cov.:

AF XY:

0.435

AC XY:

308385

AN XY:

709598

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.448

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.377

AC:

57228

AN:

151992

Hom.:

11766

Cov.:

AF XY:

0.377

AC XY:

27979

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.411

Hom.:

2467

Bravo

AF:

0.370

Asia WGS

AF:

0.295

AC:

1027

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

-0.88

CADD

Benign

0.17

DANN

Benign

0.84

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