7-154997088-A-G

Variant names:

• chr7-154997088-A-G
• rs306278
• NM_007349.4:c.216+1562T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAXIP1	NM_007349.4	c.216+1562T>C		intron_variant	Intron 2 of 20	ENST00000404141.6	NP_031375.3
PAXIP1	XM_011515982.4	c.138+1562T>C		intron_variant	Intron 2 of 20		XP_011514284.1
PAXIP1	XM_047420059.1	c.-526+1562T>C		intron_variant	Intron 2 of 20		XP_047276015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAXIP1	ENST00000404141.6	c.216+1562T>C		intron_variant	Intron 2 of 20	5	NM_007349.4	ENSP00000384048.1
PAXIP1	ENST00000419436.1	c.198+1562T>C		intron_variant	Intron 2 of 3	4		ENSP00000389849.1
PAXIP1	ENST00000457196.5	n.216+1562T>C		intron_variant	Intron 2 of 21	5		ENSP00000392011.1
PAXIP1	ENST00000473219.5	n.2156+1562T>C		intron_variant	Intron 2 of 20	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

African (AFR) AF: 0.178 AC: 7403 AN: 41486

American (AMR) AF: 0.537 AC: 8202 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2119 AN: 5166

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4818

European-Finnish (FIN) AF: 0.647 AC: 6834 AN: 10562

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38717 AN: 67938

Other (OTH) AF: 0.487 AC: 1029 AN: 2114

Alfa AF: 0.541 Hom.: 16923

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
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs306278; hg19: chr7-154788798;