Variant 19-13135193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052876.4(NACC1):c.-8-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,567,110 control chromosomes in the GnomAD database, including 1 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 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

NACC1
NM_052876.4 splice_region, intron

Scores

Splicing: ADA: 0.0001108

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98

Variant links:

Genes affected

NACC1 (HGNC:20967): (nucleus accumbens associated 1) This gene encodes a member of the BTB/POZ protein family. BTB/POZ proteins are involved in several cellular processes including proliferation, apoptosis and transcription regulation. The encoded protein is a transcriptional repressor that plays a role in stem cell self-renewal and pluripotency maintenance. The encoded protein also suppresses transcription of the candidate tumor suppressor Gadd45GIP1, and expression of this gene may play a role in the progression of multiple types of cancer. A pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Feb 2012]

NACC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-13135193-C-T is Benign according to our data. Variant chr19-13135193-C-T is described in ClinVar as [Benign]. Clinvar id is 2649370.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 264 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NACC1	NM_052876.4 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant	ENST00000292431.5	NP_443108.1	Q96RE7A0A024R7E0
NACC1	XM_005259721.4 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant		XP_005259778.1	Q96RE7A0A024R7E0
NACC1	XM_047438118.1 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant		XP_047294074.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NACC1	ENST00000292431.5 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant	1	NM_052876.4	ENSP00000292431.3	Q96RE7
NACC1	ENST00000586171.3 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant	5		ENSP00000467120.2	Q96RE7K7ENW4
NACC1	ENST00000700232.1 linkuse as main transcript	c.-8-7C>T	splice_region_variant, intron_variant			ENSP00000514870.1	Q96RE7

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

263

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000478

AC:

100

AN:

209206

Hom.:

AF XY:

0.000327

AC XY:

AN XY:

113214

show subpopulations

Gnomad AFR exome

AF:

0.00635

Gnomad AMR exome

AF:

0.0000690

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:

0.0000424

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

238

AN:

1414786

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

698298

show subpopulations

Gnomad4 AFR exome

AF:

0.00580

Gnomad4 AMR exome

AF:

0.000127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000230

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.00173

AC:

264

AN:

152324

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00611

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000946

Bravo

AF:

0.00186

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

NACC1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.021

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0020

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