chr1-4711890-C-G

Variant names:

• chr1-4711890-C-G
• rs373570588
• NM_018836.4:c.30-10C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018836.4(AJAP1):​c.30-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,516 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: AJAP1 NM_018836.4 intron
• Scores: Splicing: ADA: 0.0003623
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.30-10C>G		intron_variant	Intron 1 of 5	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.30-10C>G		intron_variant	Intron 1 of 5		NP_001035943.1
AJAP1	XM_011541786.3	c.30-10C>G		intron_variant	Intron 1 of 6		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.30-10C>G		intron_variant	Intron 1 of 5	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.30-10C>G		intron_variant	Intron 1 of 5	5		ENSP00000367432.3
AJAP1	ENST00000466761.1	n.33-10C>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321516 Hom.: 0 Cov.: 29 AF XY: 0.00000155 AC XY: 1 AN XY: 645994

African (AFR) AF: 0.00 AC: 0 AN: 26418

American (AMR) AF: 0.00 AC: 0 AN: 23214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19076

East Asian (EAS) AF: 0.00 AC: 0 AN: 32496

South Asian (SAS) AF: 0.00 AC: 0 AN: 65420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5230

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1046726

Other (OTH) AF: 0.00 AC: 0 AN: 54342

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		-0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.024
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: rs373570588; hg19: chr1-4771950;