rs2051656

Variant names:

• chr1-167776722-A-G
• rs2051656
• NM_003953.6:c.708+556A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.708+556A>G		intron_variant	Intron 5 of 5	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5	c.605+3354A>G		intron_variant	Intron 4 of 4		NP_078845.3
MPZL1	NM_001146191.2	c.258+10973A>G		intron_variant	Intron 2 of 2		NP_001139663.1
MPZL1	XM_047433610.1	c.336+556A>G		intron_variant	Intron 6 of 6		XP_047289566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.708+556A>G		intron_variant	Intron 5 of 5	1	NM_003953.6	ENSP00000352513.2

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

African (AFR) AF: 0.139 AC: 5771 AN: 41500

American (AMR) AF: 0.323 AC: 4933 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1891 AN: 5180

South Asian (SAS) AF: 0.168 AC: 811 AN: 4826

European-Finnish (FIN) AF: 0.282 AC: 2983 AN: 10572

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10420 AN: 68006

Other (OTH) AF: 0.183 AC: 387 AN: 2110

Alfa AF: 0.167 Hom.: 3933

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
PhyloP100		0.37
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: rs2051656; hg19: chr1-167745959;