7-154997088-A-G

Position:

• chr7-154997088-A-G

Variant summary

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

The NM_007349.4(PAXIP1):​c.216+1562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,024 control chromosomes in the GnomAD database, including 18,403 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 0.46 (18403 hom., cov: 32)
• Consequence: PAXIP1 NM_007349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

PAXIP1 (HGNC:8624): (PAX interacting protein 1) This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis. [provided by RefSeq, Jul 2008]

PAXIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAXIP1	NM_007349.4	c.216+1562T>C		intron_variant		ENST00000404141.6	NP_031375.3
PAXIP1	XM_011515982.4	c.138+1562T>C		intron_variant			XP_011514284.1
PAXIP1	XM_047420059.1	c.-526+1562T>C		intron_variant			XP_047276015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.216+1562T>C		intron_variant		5	NM_007349.4	ENSP00000384048.1
PAXIP1	ENST00000419436.1	c.198+1562T>C		intron_variant		4		ENSP00000389849.1
PAXIP1	ENST00000457196.5	n.216+1562T>C		intron_variant		5		ENSP00000392011.1
PAXIP1	ENST00000473219.5	n.2156+1562T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69706 AN: 151906 Hom.: 18407 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.458 AC: 69698 AN: 152024 Hom.: 18403 Cov.: 32 AF XY: 0.464 AC XY: 34442 AN XY: 74298

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.487

Alfa AF: 0.547 Hom.: 12609

Bravo AF: 0.443

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.78

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: rs306278; hg19: chr7-154788798;