Genetic Variant NM_015166.4:c.772-35C>T (chr22-50068590-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_015166.4(MLC1):c.772-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,604,718 control chromosomes in the GnomAD database, including 18,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1278 hom., cov: 31)

Exomes 𝑓: 0.15 ( 17221 hom. )

Consequence

MLC1
NM_015166.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.44

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=-0.93).

BP6

Variant 22-50068590-G-A is Benign according to our data. Variant chr22-50068590-G-A is described in ClinVar as [Benign]. Clinvar id is 262460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLC1	NM_015166.4 link	c.772-35C>T		intron_variant	Intron 9 of 11	ENST00000311597.10	NP_055981.1	Q15049-1A0A024R4V4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MLC1	ENST00000311597.10 link	c.772-35C>T	intron_variant	Intron 9 of 11	1	NM_015166.4	ENSP00000310375.6	Q15049-1
MLC1	ENST00000395876.6 link	c.772-35C>T	intron_variant	Intron 9 of 11	1		ENSP00000379216.2	Q15049-1
MLC1	ENST00000483836.1 link	n.129-35C>T	intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18576

AN:

151808

Hom.:

1278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0975

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.0855

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.138

AC:

34372

AN:

248190

Hom.:

2611

AF XY:

0.145

AC XY:

19537

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.0760

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.0879

Gnomad EAS exome

AF:

0.0967

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0948

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.149

AC:

216808

AN:

1452792

Hom.:

17221

Cov.:

AF XY:

0.152

AC XY:

109646

AN XY:

722780

show subpopulations

Gnomad4 AFR exome

AF:

0.0729

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.0839

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.0981

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.122

AC:

18582

AN:

151926

Hom.:

1278

Cov.:

AF XY:

0.123

AC XY:

9117

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0750

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.0979

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.0803

Hom.:

128

Bravo

AF:

0.124

Asia WGS

AF:

0.154

AC:

534

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Megalencephalic leukoencephalopathy with subcortical cysts 1

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.46

DANN

Benign

0.48

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