chr1-61914452-A-G

Variant names:

• chr1-61914452-A-G
• rs4915789
• NM_001350145.3:c.3493-135A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350145.3(PATJ):​c.3493-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 450,278 control chromosomes in the GnomAD database, including 99,729 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 0.64 (31577 hom., cov: 31)
  • Exomes 𝑓: 0.67 (68152 hom.)
• Consequence: PATJ NM_001350145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 4 publications found

Genes affected

PATJ (HGNC:28881): (PATJ crumbs cell polarity complex component) This gene encodes a protein with multiple PDZ domains. PDZ domains mediate protein-protein interactions, and proteins with multiple PDZ domains often organize multimeric complexes at the plasma membrane. This protein localizes to tight junctions and to the apical membrane of epithelial cells. A similar protein in Drosophila is a scaffolding protein which tethers several members of a multimeric signaling complex in photoreceptors. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATJ	NM_001350145.3	MANE Select	c.3493-135A>G		intron	N/A	NP_001337074.2
	PATJ	NM_176877.5		c.3493-135A>G		intron	N/A	NP_795352.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATJ	ENST00000642238.2	MANE Select	c.3493-135A>G		intron	N/A	ENSP00000494277.1
	PATJ	ENST00000459752.5	TSL:1	n.3607-135A>G		intron	N/A
	PATJ	ENST00000484562.5	TSL:1	n.3607-135A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97475 AN: 151844 Hom.: 31550 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.671 AC: 200244 AN: 298318 Hom.: 68152 AF XY: 0.676 AC XY: 108210 AN XY: 159996

African (AFR) AF: 0.613 AC: 4974 AN: 8120

American (AMR) AF: 0.704 AC: 7348 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 6347 AN: 8914

East Asian (EAS) AF: 0.790 AC: 15814 AN: 20026

South Asian (SAS) AF: 0.782 AC: 24586 AN: 31456

European-Finnish (FIN) AF: 0.705 AC: 21318 AN: 30224

Middle Eastern (MID) AF: 0.706 AC: 1864 AN: 2640

European-Non Finnish (NFE) AF: 0.630 AC: 107357 AN: 170494

Other (OTH) AF: 0.664 AC: 10636 AN: 16010

GnomAD4 genome AF: 0.642 AC: 97555 AN: 151960 Hom.: 31577 Cov.: 31 AF XY: 0.649 AC XY: 48180 AN XY: 74274

African (AFR) AF: 0.617 AC: 25563 AN: 41414

American (AMR) AF: 0.676 AC: 10319 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2406 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4070 AN: 5166

South Asian (SAS) AF: 0.766 AC: 3696 AN: 4824

European-Finnish (FIN) AF: 0.694 AC: 7317 AN: 10546

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42082 AN: 67974

Other (OTH) AF: 0.632 AC: 1333 AN: 2108

Alfa AF: 0.628 Hom.: 37239

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		-0.83
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4915789; hg19: chr1-62380124;