rs7928030

Variant names:

• chr11-94153672-G-C
• rs7928030
• NM_015368.4:c.321+42G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015368.4(PANX1):​c.321+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,587,884 control chromosomes in the GnomAD database, including 174,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17483 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157053 hom.)
• Consequence: PANX1 NM_015368.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.859
• Publications: 3 publications found

Genes affected

PANX1 (HGNC:8599): (pannexin 1) The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties. [provided by RefSeq, Jul 2008]

PANX1 Gene-Disease associations (from GenCC):

• oocyte maturation defect 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-94153672-G-C is Benign according to our data. Variant chr11-94153672-G-C is described in ClinVar as [Benign]. Clinvar id is 1244633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX1	NM_015368.4	c.321+42G>C		intron_variant	Intron 2 of 4	ENST00000227638.8	NP_056183.2
PANX1	XM_011542734.3	c.-352+42G>C		intron_variant	Intron 1 of 5		XP_011541036.1
PANX1	XM_047426702.1	c.-248+42G>C		intron_variant	Intron 1 of 4		XP_047282658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX1	ENST00000227638.8	c.321+42G>C		intron_variant	Intron 2 of 4	1	NM_015368.4	ENSP00000227638.3
PANX1	ENST00000436171.2	c.321+42G>C		intron_variant	Intron 2 of 4	1		ENSP00000411461.2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72351 AN: 151918 Hom.: 17455 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.477 AC: 110639 AN: 231748 AF XY: 0.463

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.417

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.464 AC: 666766 AN: 1435846 Hom.: 157053 Cov.: 26 AF XY: 0.459 AC XY: 327346 AN XY: 713906

African (AFR) AF: 0.481 AC: 15816 AN: 32902

American (AMR) AF: 0.644 AC: 27762 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 13827 AN: 25746

East Asian (EAS) AF: 0.428 AC: 16892 AN: 39448

South Asian (SAS) AF: 0.307 AC: 25957 AN: 84648

European-Finnish (FIN) AF: 0.496 AC: 23375 AN: 47118

Middle Eastern (MID) AF: 0.423 AC: 2403 AN: 5686

European-Non Finnish (NFE) AF: 0.468 AC: 513155 AN: 1097640

Other (OTH) AF: 0.463 AC: 27579 AN: 59532

GnomAD4 genome AF: 0.476 AC: 72431 AN: 152038 Hom.: 17483 Cov.: 32 AF XY: 0.477 AC XY: 35432 AN XY: 74316

African (AFR) AF: 0.481 AC: 19967 AN: 41470

American (AMR) AF: 0.578 AC: 8827 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2074 AN: 5174

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4822

European-Finnish (FIN) AF: 0.506 AC: 5343 AN: 10556

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31454 AN: 67948

Other (OTH) AF: 0.516 AC: 1088 AN: 2110

Alfa AF: 0.476 Hom.: 3396

Bravo AF: 0.489

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.59
PhyloP100		0.86
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: rs7928030; hg19: chr11-93886838; COSMIC: COSV57135053;