1-4759057-A-C

Variant names:

• chr1-4759057-A-C
• rs422988
• NM_018836.4:c.830-10796A>C

Variant summary

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

The NM_018836.4(AJAP1):​c.830-10796A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,254 control chromosomes in the GnomAD database, including 59,282 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 0.88 (59282 hom., cov: 33)
• Consequence: AJAP1 NM_018836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.830-10796A>C		intron_variant	Intron 2 of 5	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.830-10796A>C		intron_variant	Intron 2 of 5		NP_001035943.1
AJAP1	XM_011541786.3	c.830-10796A>C		intron_variant	Intron 2 of 6		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.830-10796A>C		intron_variant	Intron 2 of 5	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.830-10796A>C		intron_variant	Intron 2 of 5	5		ENSP00000367432.3

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133559 AN: 152136 Hom.: 59231 Cov.: 33

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.878 AC: 133672 AN: 152254 Hom.: 59282 Cov.: 33 AF XY: 0.871 AC XY: 64839 AN XY: 74432

African (AFR) AF: 0.939 AC: 39028 AN: 41566

American (AMR) AF: 0.857 AC: 13122 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2938 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2379 AN: 5146

South Asian (SAS) AF: 0.847 AC: 4082 AN: 4818

European-Finnish (FIN) AF: 0.830 AC: 8795 AN: 10600

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60370 AN: 68024

Other (OTH) AF: 0.884 AC: 1871 AN: 2116

Alfa AF: 0.876 Hom.: 6909

Bravo AF: 0.878

Asia WGS AF: 0.717 AC: 2494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs422988; hg19: chr1-4819117;