11-108221910-G-T

Position:

• chr11-108221910-G-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+590C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,164 control chromosomes in the GnomAD database, including 558 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 0.082 (558 hom., cov: 32)
• Consequence: NPAT NM_002519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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]

NPAT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAT	NM_002519.3	c.37+590C>A		intron_variant		ENST00000278612.9	NP_002510.2
NPAT	NM_001321307.1	c.37+590C>A		intron_variant			NP_001308236.1
NPAT	XM_011542854.3	c.37+590C>A		intron_variant			XP_011541156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAT	ENST00000278612.9	c.37+590C>A		intron_variant		1	NM_002519.3	ENSP00000278612.8
NPAT	ENST00000531384.1	n.37+590C>A		intron_variant		5		ENSP00000433497.1
NPAT	ENST00000610253.5	n.137+590C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12513 AN: 152046 Hom.: 556 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.0912

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

GnomAD4 genome AF: 0.0823 AC: 12530 AN: 152164 Hom.: 558 Cov.: 32 AF XY: 0.0800 AC XY: 5950 AN XY: 74382

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0940

Gnomad4 OTH AF: 0.0897

Alfa AF: 0.0904 Hom.: 1053

Bravo AF: 0.0856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.40

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: rs4987876; hg19: chr11-108092637;