rs137930

Positions:

• chr22-50085004-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015166.4(MLC1):​c.-59-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,541,730 control chromosomes in the GnomAD database, including 87,940 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 0.26 (6325 hom., cov: 33)
  • Exomes 𝑓: 0.33 (81615 hom.)
• Consequence: MLC1 NM_015166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4	c.-59-43A>G		intron_variant		ENST00000311597.10	NP_055981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLC1	ENST00000311597.10	c.-59-43A>G		intron_variant		1	NM_015166.4	ENSP00000310375	P1
MLC1	ENST00000395876.6	c.-59-43A>G		intron_variant		1		ENSP00000379216	P1
MLC1	ENST00000442311.1	c.-59-43A>G		intron_variant		5		ENSP00000401385

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39717 AN: 152150 Hom.: 6329 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.334 AC: 463440 AN: 1389462 Hom.: 81615 Cov.: 29 AF XY: 0.331 AC XY: 227626 AN XY: 687068

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.0213

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.261 AC: 39715 AN: 152268 Hom.: 6325 Cov.: 33 AF XY: 0.260 AC XY: 19391 AN XY: 74440

Gnomad4 AFR AF: 0.0965

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.232

Alfa AF: 0.277 Hom.: 1407

Bravo AF: 0.246

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs137930; hg19: chr22-50523433;