rs1659506

chr16-4634447-G-Achr16-4634447-G-Cchr16-4634447-G-T

Variant summary

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

The NM_015246.4(MGRN1):c.88+9399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,560 control chromosomes in the GnomAD database, including 5,808 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 0.25 (5801 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: MGRN1 NM_015246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77

Genes affected

MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGRN1	NM_015246.4	c.88+9399G>A		intron_variant		ENST00000262370.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGRN1	ENST00000262370.12	c.88+9399G>A		intron_variant		1	NM_015246.4	A1
	ENST00000569678.1	n.1425C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38219 AN: 152070 Hom.: 5789 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.172 AC: 64 AN: 372 Hom.: 7 Cov.: 0 AF XY: 0.162 AC XY: 44 AN XY: 272

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0769

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.251 AC: 38262 AN: 152188 Hom.: 5801 Cov.: 32 AF XY: 0.246 AC XY: 18268 AN XY: 74408

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.227

Alfa AF: 0.211 Hom.: 3039

Bravo AF: 0.260

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.19
Dann	Benign	0.74

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: rs1659506; hg19: chr16-4684448; COSMIC: COSV52153107; COSMIC: COSV52153107;