10-113879639-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198514.4(NHLRC2):c.853G>A(p.Ala285Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00166 in 1,572,724 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (23 hom.)
• Consequence: NHLRC2 NM_198514.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.35

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01260677).
• BP6: Variant 10-113879639-G-A is Benign according to our data. Variant chr10-113879639-G-A is described in ClinVar as [Benign]. Clinvar id is 3034232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00873 (1328/152148) while in subpopulation AFR AF= 0.0305 (1266/41528). AF 95% confidence interval is 0.0291. There are 20 homozygotes in gnomad4. There are 633 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHLRC2	NM_198514.4	c.853G>A	p.Ala285Thr	missense_variant	4/11	ENST00000369301.3
NHLRC2	XM_011539769.4	c.853G>A	p.Ala285Thr	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHLRC2	ENST00000369301.3	c.853G>A	p.Ala285Thr	missense_variant	4/11	2	NM_198514.4	P1

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1323 AN: 152032 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

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: 0.0000736

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00216 AC: 525 AN: 242748 Hom.: 5 AF XY: 0.00162 AC XY: 213 AN XY: 131336

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000849

GnomAD4 exome AF: 0.000906 AC: 1287 AN: 1420576 Hom.: 23 Cov.: 24 AF XY: 0.000753 AC XY: 534 AN XY: 708832

Gnomad4 AFR exome AF: 0.0337

Gnomad4 AMR exome AF: 0.00191

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000834

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00873 AC: 1328 AN: 152148 Hom.: 20 Cov.: 32 AF XY: 0.00851 AC XY: 633 AN XY: 74374

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00103 Hom.: 2

Bravo AF: 0.00996

ESP6500AA AF: 0.0286 AC: 126

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00279 AC: 338

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NHLRC2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 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
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.48
Sift	Benign	0.036	D
Sift4G	Benign	0.21	T
Polyphen		0.84	P
Vest4		0.78
MVP		0.93
MPC		0.19
ClinPred		0.039	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.79

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

Other links and lift over

dbSNP: rs75758714; hg19: chr10-115639398; COSMIC: COSV65175056;