rs11568184

Variant summary

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

The NM_015166.4(MLC1):​c.895-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,574,750 control chromosomes in the GnomAD database, including 17,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1260 hom., cov: 34)
Exomes 𝑓: 0.15 ( 16446 hom. )

Consequence

MLC1
NM_015166.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.733
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]

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=-0.82).
BP6
Variant 22-50064221-G-A is Benign according to our data. Variant chr22-50064221-G-A is described in ClinVar as [Benign]. Clinvar id is 262461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MLC1NM_015166.4 linkuse as main transcriptc.895-23C>T intron_variant ENST00000311597.10 NP_055981.1 Q15049-1A0A024R4V4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MLC1ENST00000311597.10 linkuse as main transcriptc.895-23C>T intron_variant 1 NM_015166.4 ENSP00000310375.6 Q15049-1
MLC1ENST00000395876.6 linkuse as main transcriptc.895-23C>T intron_variant 1 ENSP00000379216.2 Q15049-1
MLC1ENST00000483836.1 linkuse as main transcriptn.252-23C>T intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.122
AC:
18565
AN:
152094
Hom.:
1259
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0748
Gnomad AMI
AF:
0.123
Gnomad AMR
AF:
0.174
Gnomad ASJ
AF:
0.0775
Gnomad EAS
AF:
0.0975
Gnomad SAS
AF:
0.229
Gnomad FIN
AF:
0.0857
Gnomad MID
AF:
0.102
Gnomad NFE
AF:
0.141
Gnomad OTH
AF:
0.148
GnomAD3 exomes
AF:
0.126
AC:
24253
AN:
192352
Hom.:
1690
AF XY:
0.132
AC XY:
13979
AN XY:
105544
show subpopulations
Gnomad AFR exome
AF:
0.0639
Gnomad AMR exome
AF:
0.124
Gnomad ASJ exome
AF:
0.0830
Gnomad EAS exome
AF:
0.0854
Gnomad SAS exome
AF:
0.207
Gnomad FIN exome
AF:
0.0778
Gnomad NFE exome
AF:
0.127
Gnomad OTH exome
AF:
0.133
GnomAD4 exome
AF:
0.149
AC:
211760
AN:
1422536
Hom.:
16446
Cov.:
38
AF XY:
0.151
AC XY:
106589
AN XY:
706068
show subpopulations
Gnomad4 AFR exome
AF:
0.0723
Gnomad4 AMR exome
AF:
0.133
Gnomad4 ASJ exome
AF:
0.0836
Gnomad4 EAS exome
AF:
0.100
Gnomad4 SAS exome
AF:
0.218
Gnomad4 FIN exome
AF:
0.0956
Gnomad4 NFE exome
AF:
0.152
Gnomad4 OTH exome
AF:
0.142
GnomAD4 genome
AF:
0.122
AC:
18572
AN:
152214
Hom.:
1260
Cov.:
34
AF XY:
0.123
AC XY:
9117
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0749
Gnomad4 AMR
AF:
0.174
Gnomad4 ASJ
AF:
0.0775
Gnomad4 EAS
AF:
0.0979
Gnomad4 SAS
AF:
0.229
Gnomad4 FIN
AF:
0.0857
Gnomad4 NFE
AF:
0.141
Gnomad4 OTH
AF:
0.146
Alfa
AF:
0.121
Hom.:
209
Bravo
AF:
0.124
Asia WGS
AF:
0.155
AC:
538
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 13, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Megalencephalic leukoencephalopathy with subcortical cysts 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJun 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.7
DANN
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs11568184; hg19: chr22-50502650; API