1-4657331-A-G

Position:

• chr1-4657331-A-G

Variant summary

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

The NM_018836.4(AJAP1):​c.29+1877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,242 control chromosomes in the GnomAD database, including 2,628 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 0.17 (2628 hom., cov: 31)
• Consequence: AJAP1 NM_018836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.29+1877A>G		intron_variant		ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.29+1877A>G		intron_variant			NP_001035943.1
AJAP1	XM_011541786.3	c.29+1877A>G		intron_variant			XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.29+1877A>G		intron_variant		1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.29+1877A>G		intron_variant		5		ENSP00000367432.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25433 AN: 151126 Hom.: 2630 Cov.: 31

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25425 AN: 151242 Hom.: 2628 Cov.: 31 AF XY: 0.174 AC XY: 12863 AN XY: 73852

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.143

Alfa AF: 0.197 Hom.: 4370

Bravo AF: 0.148

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1483198; hg19: chr1-4717391;