rs183460

chr11-108219983-A-Cchr11-108219983-A-Gchr11-108219983-A-T

Variant summary

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

The NM_002519.3(NPAT):c.37+2517T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,072 control chromosomes in the GnomAD database, including 21,913 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 0.53 (21913 hom., cov: 33)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

NPAT (HGNC:7896): (nuclear protein, coactivator of histone transcription) Enables protein C-terminus binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription involved in G1/S transition of mitotic cell cycle. Located in Cajal body; Gemini of coiled bodies; and cytoplasm. [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 (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAT	NM_002519.3	c.37+2517T>G		intron_variant		ENST00000278612.9
NPAT	NM_001321307.1	c.37+2517T>G		intron_variant
NPAT	XM_011542854.3	c.37+2517T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAT	ENST00000278612.9	c.37+2517T>G		intron_variant		1	NM_002519.3	P1
NPAT	ENST00000531384.1	c.37+2517T>G		intron_variant, NMD_transcript_variant		5
NPAT	ENST00000610253.5	n.137+2517T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80017 AN: 151954 Hom.: 21902 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.526 AC: 80053 AN: 152072 Hom.: 21913 Cov.: 33 AF XY: 0.535 AC XY: 39792 AN XY: 74342

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.561

Alfa AF: 0.482 Hom.: 2692

Bravo AF: 0.516

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	10
Dann	Benign	0.57

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: rs183460; hg19: chr11-108090710;