Variant 10-113879701-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198514.4(NHLRC2):c.909+6T>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,448,580 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.014 ( 184 hom. )

Consequence

NHLRC2
NM_198514.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.01105

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.684

Variant links:

Genes affected

NHLRC2 (HGNC:24731): (NHL repeat containing 2) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NHLRC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 10-113879701-T-A is Benign according to our data. Variant chr10-113879701-T-A is described in ClinVar as [Benign]. Clinvar id is 3041791.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1833/152156) while in subpopulation NFE AF= 0.0157 (1064/67960). AF 95% confidence interval is 0.0149. There are 18 homozygotes in gnomad4. There are 963 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHLRC2	NM_198514.4 linkuse as main transcript	c.909+6T>A		splice_donor_region_variant, intron_variant		ENST00000369301.3
NHLRC2	XM_011539769.4 linkuse as main transcript	c.909+6T>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHLRC2	ENST00000369301.3 linkuse as main transcript	c.909+6T>A		splice_donor_region_variant, intron_variant		2	NM_198514.4	P1	Q8NBF2-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0411

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0155

AC:

2988

AN:

192502

Hom.:

AF XY:

0.0154

AC XY:

1635

AN XY:

106190

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00772

Gnomad ASJ exome

AF:

0.00345

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0213

GnomAD4 exome

AF:

0.0141

AC:

18290

AN:

1296424

Hom.:

184

Cov.:

AF XY:

0.0138

AC XY:

8984

AN XY:

650024

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

Gnomad4 AMR exome

AF:

0.00744

Gnomad4 ASJ exome

AF:

0.00336

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0120

AC:

1833

AN:

152156

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

963

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00289

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0411

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00978

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NHLRC2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.011

dbscSNV1_RF

Benign

0.11

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