10-113901406-G-A

Variant names:

• chr10-113901406-G-A
• rs4345919
• NM_198514.4:c.1140-260G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198514.4(NHLRC2):​c.1140-260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,066 control chromosomes in the GnomAD database, including 1,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1367 hom., cov: 32)
• Consequence: NHLRC2 NM_198514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 3 publications found

Genes affected

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

NHLRC2 Gene-Disease associations (from GenCC):

• fibrosis, neurodegeneration, and cerebral angiomatosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	NM_198514.4	MANE Select	c.1140-260G>A		intron	N/A	NP_940916.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	ENST00000369301.3	TSL:2 MANE Select	c.1140-260G>A		intron	N/A	ENSP00000358307.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18527 AN: 151948 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18515 AN: 152066 Hom.: 1367 Cov.: 32 AF XY: 0.124 AC XY: 9242 AN XY: 74314

African (AFR) AF: 0.0576 AC: 2390 AN: 41496

American (AMR) AF: 0.0948 AC: 1448 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1518 AN: 5168

South Asian (SAS) AF: 0.235 AC: 1136 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1590 AN: 10540

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9543 AN: 67974

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.134 Hom.: 2485

Bravo AF: 0.114

Asia WGS AF: 0.229 AC: 798 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0030
DANN	Benign	0.33
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4345919; hg19: chr10-115661165;