Variant chr1-16440791-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018090.5(NECAP2):c.30C>G(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,614,140 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 64 hom. )

Consequence

NECAP2
NM_018090.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.78

Variant links:

Genes affected

NECAP2 (HGNC:25528): (NECAP endocytosis associated 2) This gene likely encodes a member of the adaptin-ear-binding coat-associated protein family. Studies of a similar protein in rat suggest a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

NECAP2 links:

NECAP2 (HGNC:):

NECAP2 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=-0.85).

BP6

Variant 1-16440791-C-G is Benign according to our data. Variant chr1-16440791-C-G is described in ClinVar as [Benign]. Clinvar id is 790474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAP2	NM_018090.5 linkuse as main transcript	c.30C>G	p.Leu10Leu	synonymous_variant	1/8	ENST00000337132.10	NP_060560.1	Q9NVZ3-1
NECAP2	NM_001145277.2 linkuse as main transcript	c.30C>G	p.Leu10Leu	synonymous_variant	1/7		NP_001138749.1	Q9NVZ3-2
NECAP2	XM_047424715.1 linkuse as main transcript	c.30C>G	p.Leu10Leu	synonymous_variant	1/7		XP_047280671.1
NECAP2	NM_001145278.2 linkuse as main transcript	c.14+16C>G		intron_variant			NP_001138750.1	Q9NVZ3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAP2	ENST00000337132.10 linkuse as main transcript	c.30C>G	p.Leu10Leu	synonymous_variant	1/8	1	NM_018090.5	ENSP00000338746.5		Q9NVZ3-1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2468

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00408

AC:

1023

AN:

251004

Hom.:

AF XY:

0.00298

AC XY:

405

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0550

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00170

AC:

2478

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1035

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0595

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000122

Gnomad4 OTH exome

AF:

0.00339

GnomAD4 genome

AF:

0.0163

AC:

2488

AN:

152286

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1181

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.0185

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.2

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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