1-167749262-A-G

Variant names:

• chr1-167749262-A-G
• rs4145462
• NM_003953.6:c.92-16321A>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.92-16321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 152,342 control chromosomes in the GnomAD database, including 73,959 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 0.99 (73959 hom., cov: 32)
• Consequence: MPZL1 NM_003953.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 8 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 = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.92-16321A>G		intron_variant	Intron 1 of 5	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5	c.92-16321A>G		intron_variant	Intron 1 of 4		NP_078845.3
MPZL1	NM_001146191.2	c.92-16321A>G		intron_variant	Intron 1 of 2		NP_001139663.1
MPZL1	XM_047433610.1	c.-282+16024A>G		intron_variant	Intron 2 of 6		XP_047289566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.92-16321A>G		intron_variant	Intron 1 of 5	1	NM_003953.6	ENSP00000352513.2

Frequencies

GnomAD3 genomes AF: 0.985 AC: 149988 AN: 152224 Hom.: 73898 Cov.: 32

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.984

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

GnomAD4 genome AF: 0.985 AC: 150108 AN: 152342 Hom.: 73959 Cov.: 32 AF XY: 0.986 AC XY: 73492 AN XY: 74498

African (AFR) AF: 0.995 AC: 41378 AN: 41578

American (AMR) AF: 0.991 AC: 15157 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3417 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.991 AC: 4789 AN: 4832

European-Finnish (FIN) AF: 0.993 AC: 10554 AN: 10624

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.975 AC: 66341 AN: 68028

Other (OTH) AF: 0.984 AC: 2079 AN: 2112

Alfa AF: 0.979 Hom.: 94048

Bravo AF: 0.986

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.76
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: rs4145462; hg19: chr1-167718499;