rs2072902

Positions:

• chr1-4769821-G-A

Variant summary

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

The NM_018836.4(AJAP1):​c.830-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,588,638 control chromosomes in the GnomAD database, including 683 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 0.0053 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (635 hom.)
• Consequence: AJAP1 NM_018836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

Genes affected

AJAP1 (HGNC:30801): (adherens junctions associated protein 1) Enables beta-catenin binding activity. Involved in negative regulation of cell-matrix adhesion; negative regulation of wound healing; and regulation of polarized epithelial cell differentiation. Located in several cellular components, including adherens junction; basolateral plasma membrane; and cell-cell contact zone. Is spanning component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.830-32G>A		intron_variant		ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.830-32G>A		intron_variant			NP_001035943.1
AJAP1	XM_011541786.3	c.830-32G>A		intron_variant			XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.830-32G>A		intron_variant		1	NM_018836.4	ENSP00000367433	P1
AJAP1	ENST00000378190.7	c.830-32G>A		intron_variant		5		ENSP00000367432	P1

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 800 AN: 151902 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.00230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.0146 AC: 3677 AN: 251218 Hom.: 223 AF XY: 0.0193 AC XY: 2627 AN XY: 135792

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0150

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00761 AC: 10935 AN: 1436616 Hom.: 635 Cov.: 29 AF XY: 0.0105 AC XY: 7494 AN XY: 716596

Gnomad4 AFR exome AF: 0.00200

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0327

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000881

Gnomad4 OTH exome AF: 0.00921

GnomAD4 genome AF: 0.00530 AC: 806 AN: 152022 Hom.: 48 Cov.: 33 AF XY: 0.00724 AC XY: 538 AN XY: 74316

Gnomad4 AFR AF: 0.00232

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00162 Hom.: 3

Bravo AF: 0.00217

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072902; hg19: chr1-4829881;