rs11568171

Variant names:

• chr22-50084988-G-A
• rs11568171
• NM_015166.4:c.-59-27C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50084988-G-A
• chr22-50084988-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376472.1(MLC1):​c.-86C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 1,569,394 control chromosomes in the GnomAD database, including 7,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (503 hom., cov: 33)
  • Exomes 𝑓: 0.097 (7141 hom.)
• Consequence: MLC1 NM_001376472.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• megalencephalic leukoencephalopathy with subcortical cysts 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P, Ambry Genetics
• megalencephalic leukoencephalopathy with subcortical cysts

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376472.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLC1	NM_015166.4	MANE Select	c.-59-27C>T		intron	N/A	NP_055981.1	Q15049-1
	MLC1	NM_001376472.1		c.-86C>T		5_prime_UTR	Exon 1 of 11	NP_001363401.1	Q15049-1
	MLC1	NM_001376477.1		c.-86C>T		5_prime_UTR	Exon 1 of 12	NP_001363406.1	Q15049-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLC1	ENST00000311597.10	TSL:1 MANE Select	c.-59-27C>T		intron	N/A	ENSP00000310375.6	Q15049-1
	MLC1	ENST00000395876.6	TSL:1	c.-59-27C>T		intron	N/A	ENSP00000379216.2	Q15049-1
	MLC1	ENST00000879274.1		c.-86C>T		5_prime_UTR	Exon 1 of 11	ENSP00000549333.1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11404 AN: 152186 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0965

GnomAD4 exome AF: 0.0970 AC: 137523 AN: 1417090 Hom.: 7141 Cov.: 31 AF XY: 0.0996 AC XY: 70017 AN XY: 703048

African (AFR) AF: 0.0423 AC: 1390 AN: 32838

American (AMR) AF: 0.0718 AC: 2844 AN: 39608

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 1214 AN: 25492

East Asian (EAS) AF: 0.0806 AC: 3107 AN: 38548

South Asian (SAS) AF: 0.167 AC: 13863 AN: 82996

European-Finnish (FIN) AF: 0.0723 AC: 2709 AN: 37446

Middle Eastern (MID) AF: 0.114 AC: 572 AN: 5036

European-Non Finnish (NFE) AF: 0.0969 AC: 106148 AN: 1095960

Other (OTH) AF: 0.0959 AC: 5676 AN: 59166

GnomAD4 genome AF: 0.0749 AC: 11407 AN: 152304 Hom.: 503 Cov.: 33 AF XY: 0.0754 AC XY: 5615 AN XY: 74468

African (AFR) AF: 0.0407 AC: 1690 AN: 41570

American (AMR) AF: 0.0837 AC: 1281 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3470

East Asian (EAS) AF: 0.0698 AC: 362 AN: 5186

South Asian (SAS) AF: 0.164 AC: 794 AN: 4830

European-Finnish (FIN) AF: 0.0648 AC: 687 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0907 AC: 6168 AN: 68020

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0394 Hom.: 50

Bravo AF: 0.0744

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.59
PhyloP100		-0.65
BranchPoint Hunter		1.0
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11568171; hg19: chr22-50523417;