rs327518

Variant names:

• chr7-127611738-G-A
• rs327518
• NM_001366110.1:c.772-62C>T

Variant summary

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

The NM_001366110.1(PAX4):​c.772-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,601,966 control chromosomes in the GnomAD database, including 117,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8438 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109371 hom.)
• Consequence: PAX4 NM_001366110.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 15 publications found

Genes affected

PAX4 (HGNC:8618): (paired box 4) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]

PAX4 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• diabetes mellitus, noninsulin-dependent

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young type 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-127611738-G-A is Benign according to our data. Variant chr7-127611738-G-A is described in ClinVar as Benign. ClinVar VariationId is 1292426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX4	NM_001366110.1	MANE Select	c.772-62C>T		intron	N/A	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.772-62C>T		intron	N/A	NP_001353040.1	J3KPG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX4	ENST00000639438.3	TSL:5 MANE Select	c.772-62C>T		intron	N/A	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000378740.6	TSL:1	c.772-62C>T		intron	N/A	ENSP00000368014.4	J3KPG0
	PAX4	ENST00000341640.6	TSL:1	c.748-62C>T		intron	N/A	ENSP00000339906.2	O43316-4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46075 AN: 151862 Hom.: 8432 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.381 AC: 551964 AN: 1450006 Hom.: 109371 Cov.: 49 AF XY: 0.379 AC XY: 273315 AN XY: 721532

African (AFR) AF: 0.105 AC: 3525 AN: 33432

American (AMR) AF: 0.442 AC: 19712 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12919 AN: 26120

East Asian (EAS) AF: 0.106 AC: 4198 AN: 39694

South Asian (SAS) AF: 0.301 AC: 25916 AN: 86064

European-Finnish (FIN) AF: 0.292 AC: 12587 AN: 43118

Middle Eastern (MID) AF: 0.430 AC: 2301 AN: 5350

European-Non Finnish (NFE) AF: 0.403 AC: 448231 AN: 1111424

Other (OTH) AF: 0.375 AC: 22575 AN: 60210

GnomAD4 genome AF: 0.303 AC: 46091 AN: 151960 Hom.: 8438 Cov.: 32 AF XY: 0.299 AC XY: 22207 AN XY: 74252

African (AFR) AF: 0.114 AC: 4707 AN: 41454

American (AMR) AF: 0.401 AC: 6122 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.100 AC: 518 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1439 AN: 4796

European-Finnish (FIN) AF: 0.296 AC: 3114 AN: 10536

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27260 AN: 67956

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.369 Hom.: 28830

Bravo AF: 0.307

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.51
PhyloP100		-1.1
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: rs327518; hg19: chr7-127251792; COSMIC: COSV58388384; COSMIC: COSV58388384;