Variant 5-71012424-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004536.3(NAIP):c.492G>A(p.Ala164Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,610,560 control chromosomes in the GnomAD database, including 497,378 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 0.83 ( 52656 hom., cov: 33)

Exomes 𝑓: 0.77 ( 444722 hom. )

Consequence

NAIP
NM_004536.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

NAIP (HGNC:7634): (NLR family apoptosis inhibitory protein) This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This copy of the gene is full length; additional copies with truncations and internal deletions are also present in this region of chromosome 5q13. It is thought that this gene is a modifier of spinal muscular atrophy caused by mutations in a neighboring gene, SMN1. The protein encoded by this gene contains regions of homology to two baculovirus inhibitor of apoptosis proteins, and it is able to suppress apoptosis induced by various signals. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

NAIP links:

NAIP (HGNC:):

NAIP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAIP	NM_004536.3 linkuse as main transcript	c.492G>A	p.Ala164Ala	synonymous_variant	4/17	ENST00000517649.6	NP_004527.2	Q13075-1
NAIP	NM_001346870.2 linkuse as main transcript	c.492G>A	p.Ala164Ala	synonymous_variant	4/17		NP_001333799.1	Q13075-1
NAIP	NM_022892.2 linkuse as main transcript	c.182+8235G>A		intron_variant			NP_075043.1	Q13075-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAIP	ENST00000517649.6 linkuse as main transcript	c.492G>A	p.Ala164Ala	synonymous_variant	4/17	1	NM_004536.3	ENSP00000428657.2		Q13075-1

Frequencies

GnomAD3 genomes

AF:

0.826

AC:

124773

AN:

151046

Hom.:

52589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.949

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.900

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.827

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.779

GnomAD3 exomes

AF:

0.801

AC:

201116

AN:

251000

Hom.:

82283

AF XY:

0.794

AC XY:

107637

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.873

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.905

Gnomad SAS exome

AF:

0.803

Gnomad FIN exome

AF:

0.827

Gnomad NFE exome

AF:

0.754

Gnomad OTH exome

AF:

0.765

GnomAD4 exome

AF:

0.773

AC:

1127770

AN:

1459396

Hom.:

444722

Cov.:

AF XY:

0.772

AC XY:

560410

AN XY:

726062

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.867

Gnomad4 ASJ exome

AF:

0.620

Gnomad4 EAS exome

AF:

0.878

Gnomad4 SAS exome

AF:

0.802

Gnomad4 FIN exome

AF:

0.826

Gnomad4 NFE exome

AF:

0.759

Gnomad4 OTH exome

AF:

0.772

GnomAD4 genome

AF:

0.826

AC:

124903

AN:

151164

Hom.:

52656

Cov.:

AF XY:

0.828

AC XY:

61156

AN XY:

73844

show subpopulations

Gnomad4 AFR

AF:

0.949

Gnomad4 AMR

AF:

0.835

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.900

Gnomad4 SAS

AF:

0.819

Gnomad4 FIN

AF:

0.827

Gnomad4 NFE

AF:

0.758

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.776

Hom.:

26445

Bravo

AF:

0.832

Asia WGS

AF:

0.893

AC:

3108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.1

DANN

Benign

0.37

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over