rs2273635

Positions:

• chr14-24411514-T-A
• chr14-24411514-T-G

Variant summary

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

The NM_025081.3(NYNRIN):​c.2642+64T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,392,164 control chromosomes in the GnomAD database, including 635 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 0.013 (73 hom., cov: 32)
  • Exomes 𝑓: 0.010 (562 hom.)
• Consequence: NYNRIN NM_025081.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

Genes affected

NYNRIN (HGNC:20165): (NYN domain and retroviral integrase containing) Predicted to enable endoribonuclease activity and mRNA binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, endonucleolytic. Predicted to be integral component of membrane. Predicted to be active in cytoplasmic ribonucleoprotein granule and nucleus. [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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYNRIN	NM_025081.3	c.2642+64T>A		intron_variant		ENST00000382554.4	NP_079357.2
NYNRIN	XM_011537016.2	c.-1176T>A		5_prime_UTR_variant	1/4		XP_011535318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYNRIN	ENST00000382554.4	c.2642+64T>A		intron_variant		5	NM_025081.3	ENSP00000371994.3

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1986 AN: 151974 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000898

Gnomad OTH AF: 0.00768

GnomAD4 exome AF: 0.0100 AC: 12450 AN: 1240074 Hom.: 562 AF XY: 0.0115 AC XY: 7223 AN XY: 627494

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0622

Gnomad4 FIN exome AF: 0.00349

Gnomad4 NFE exome AF: 0.000560

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0130 AC: 1978 AN: 152090 Hom.: 73 Cov.: 32 AF XY: 0.0150 AC XY: 1112 AN XY: 74338

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.000898

Gnomad4 OTH AF: 0.00713

Alfa AF: 0.00540 Hom.: 4

Bravo AF: 0.0129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.2
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2273635; hg19: chr14-24880720;