Variant 5-71012816-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004536.3(NAIP):c.100T>C(p.Leu34Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,611,826 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 195 hom. )

Consequence

NAIP
NM_004536.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.980

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-71012816-A-G is Benign according to our data. Variant chr5-71012816-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655507.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.98 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAIP	NM_004536.3 linkuse as main transcript	c.100T>C	p.Leu34Leu	synonymous_variant	4/17	ENST00000517649.6	NP_004527.2	Q13075-1
NAIP	NM_001346870.2 linkuse as main transcript	c.100T>C	p.Leu34Leu	synonymous_variant	4/17		NP_001333799.1	Q13075-1
NAIP	NM_022892.2 linkuse as main transcript	c.182+7843T>C		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.100T>C	p.Leu34Leu	synonymous_variant	4/17	1	NM_004536.3	ENSP00000428657.2		Q13075-1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

151574

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000800

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000665

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00248

AC:

623

AN:

251094

Hom.:

AF XY:

0.00239

AC XY:

325

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000788

Gnomad NFE exome

AF:

0.00439

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00384

AC:

5605

AN:

1460134

Hom.:

195

Cov.:

AF XY:

0.00369

AC XY:

2681

AN XY:

726408

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.00468

Gnomad4 OTH exome

AF:

0.00341

GnomAD4 genome

AF:

0.00239

AC:

362

AN:

151692

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

149

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.000797

Gnomad4 AMR

AF:

0.00270

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000665

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.00269

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NAIP: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

DANN

Benign

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over