rs2051656

Positions:

• chr1-167776722-A-G

Variant summary

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

The NM_003953.6(MPZL1):​c.708+556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,156 control chromosomes in the GnomAD database, including 3,048 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 0.18 (3048 hom., cov: 32)
• Consequence: MPZL1 NM_003953.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

Genes affected

MPZL1 (HGNC:7226): (myelin protein zero like 1) Predicted to enable structural molecule activity. Predicted to be involved in cell-cell signaling and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within positive regulation of cell migration. Located in cell surface and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.708+556A>G		intron_variant		ENST00000359523.7	NP_003944.1
MPZL1	NM_001146191.2	c.258+10973A>G		intron_variant			NP_001139663.1
MPZL1	NM_024569.5	c.605+3354A>G		intron_variant			NP_078845.3
MPZL1	XM_047433610.1	c.336+556A>G		intron_variant			XP_047289566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.708+556A>G		intron_variant		1	NM_003953.6	ENSP00000352513	P3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27826 AN: 152038 Hom.: 3039 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.183 AC: 27855 AN: 152156 Hom.: 3048 Cov.: 32 AF XY: 0.192 AC XY: 14277 AN XY: 74380

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.183

Alfa AF: 0.172 Hom.: 1250

Bravo AF: 0.191

Asia WGS AF: 0.272 AC: 946 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.73

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: rs2051656; hg19: chr1-167745959;