Variant 15-90266396-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001033088.3(NGRN):c.273A>C(p.Ile91Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,612,230 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 14 hom. )

Consequence

NGRN
NM_001033088.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0002167

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.624

Variant links:

Genes affected

NGRN (HGNC:18077): (neugrin, neurite outgrowth associated) Enables rRNA binding activity. Involved in positive regulation of mitochondrial translation. Located in several cellular components, including intercellular bridge; mitotic spindle; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

NGRN links:

ENSG00000275674 (HGNC:):

ENSG00000275674 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 15-90266396-A-C is Benign according to our data. Variant chr15-90266396-A-C is described in ClinVar as [Benign]. Clinvar id is 776942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.624 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0087 (1325/152326) while in subpopulation AFR AF= 0.0308 (1281/41564). AF 95% confidence interval is 0.0294. There are 20 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGRN	NM_001033088.3 link	c.273A>C	p.Ile91Ile	splice_region_variant, synonymous_variant	2/3	ENST00000379095.5	NP_001028260.2	Q9NPE2-2
NGRN	NR_028052.1 link	n.734A>C		splice_region_variant, non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NGRN	ENST00000379095.5 link	c.273A>C	p.Ile91Ile	splice_region_variant, synonymous_variant	2/3	1	NM_001033088.3	ENSP00000368389.4	Q9NPE2-2
ENSG00000275674	ENST00000622269.1 link	c.78A>C	p.Ile26Ile	splice_region_variant, synonymous_variant	1/4	3		ENSP00000479373.1	A0A087WVE0
ENSG00000261147	ENST00000561573.1 link	n.*1897A>C		splice_region_variant, non_coding_transcript_exon_variant	12/13	2		ENSP00000456615.1	H3BSA7
ENSG00000261147	ENST00000561573.1 link	n.*1897A>C		3_prime_UTR_variant	12/13	2		ENSP00000456615.1	H3BSA7

Frequencies

GnomAD3 genomes

AF:

0.00863

AC:

1314

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00210

AC:

517

AN:

246292

Hom.:

AF XY:

0.00155

AC XY:

207

AN XY:

133490

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.000851

AC:

1242

AN:

1459904

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

495

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.00870

AC:

1325

AN:

152326

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

615

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00403

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over