rs2419857

Positions:

• chr10-113857617-G-A
• chr10-113857617-G-C
• chr10-113857617-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198514.4(NHLRC2):​c.179-911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,008 control chromosomes in the GnomAD database, including 13,585 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 0.39 (13585 hom., cov: 32)
• Consequence: NHLRC2 NM_198514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHLRC2	NM_198514.4	c.179-911G>A		intron_variant		ENST00000369301.3	NP_940916.2
NHLRC2	XM_011539769.4	c.179-911G>A		intron_variant			XP_011538071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHLRC2	ENST00000369301.3	c.179-911G>A		intron_variant		2	NM_198514.4	ENSP00000358307	P1
NHLRC2	ENST00000468890.1	n.228-911G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59492 AN: 151890 Hom.: 13579 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.391 AC: 59488 AN: 152008 Hom.: 13585 Cov.: 32 AF XY: 0.395 AC XY: 29323 AN XY: 74300

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.449

Alfa AF: 0.467 Hom.: 9518

Bravo AF: 0.391

Asia WGS AF: 0.452 AC: 1567 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.27

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: rs2419857; hg19: chr10-115617376;