chr10-113858487-T-C

Position:

• chr10-113858487-T-C

Variant summary

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

The NM_198514.4(NHLRC2):​c.179-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,419,310 control chromosomes in the GnomAD database, including 57,063 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 0.25 (5185 hom., cov: 32)
  • Exomes 𝑓: 0.28 (51878 hom.)
• Consequence: NHLRC2 NM_198514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHLRC2	NM_198514.4	c.179-41T>C		intron_variant		ENST00000369301.3
NHLRC2	XM_011539769.4	c.179-41T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHLRC2	ENST00000369301.3	c.179-41T>C		intron_variant		2	NM_198514.4	P1
NHLRC2	ENST00000468890.1	n.228-41T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38063 AN: 151888 Hom.: 5180 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.224

GnomAD3 exomes AF: 0.282 AC: 55952 AN: 198354 Hom.: 8144 AF XY: 0.279 AC XY: 30164 AN XY: 107954

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.333

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.397

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.282 AC: 357378 AN: 1267302 Hom.: 51878 Cov.: 17 AF XY: 0.280 AC XY: 178053 AN XY: 635602

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.250 AC: 38075 AN: 152008 Hom.: 5185 Cov.: 32 AF XY: 0.253 AC XY: 18789 AN XY: 74272

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.222

Alfa AF: 0.262 Hom.: 1787

Bravo AF: 0.239

Asia WGS AF: 0.253 AC: 877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.54

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: rs2301180; hg19: chr10-115618246;