chr1-84970779-A-T

Variant names:

• chr1-84970779-A-T
• rs668860
• NM_153259.4:c.78-5071T>A

Variant summary

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

The NM_153259.4(MCOLN2):​c.78-5071T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,008 control chromosomes in the GnomAD database, including 19,715 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 0.51 (19715 hom., cov: 32)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 1 publications found

Genes affected

MCOLN2 (HGNC:13357): (mucolipin TRP cation channel 2) Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN2	NM_153259.4	c.78-5071T>A		intron_variant	Intron 1 of 13	ENST00000370608.8	NP_694991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN2	ENST00000370608.8	c.78-5071T>A		intron_variant	Intron 1 of 13	1	NM_153259.4	ENSP00000359640.3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76755 AN: 151888 Hom.: 19687 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.492

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.505 AC: 76837 AN: 152008 Hom.: 19715 Cov.: 32 AF XY: 0.505 AC XY: 37552 AN XY: 74322

African (AFR) AF: 0.550 AC: 22775 AN: 41436

American (AMR) AF: 0.512 AC: 7824 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3315 AN: 5170

South Asian (SAS) AF: 0.500 AC: 2410 AN: 4818

European-Finnish (FIN) AF: 0.425 AC: 4487 AN: 10560

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33180 AN: 67952

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.358 Hom.: 904

Bravo AF: 0.512

Asia WGS AF: 0.589 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.50
PhyloP100		-0.93
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: rs668860; hg19: chr1-85436462;