1-4712475-G-A

Position:

• chr1-4712475-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018836.4(AJAP1):​c.605G>A​(p.Gly202Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,611,642 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (73 hom.)
• Consequence: AJAP1 NM_018836.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067177415).
• BP6: Variant 1-4712475-G-A is Benign according to our data. Variant chr1-4712475-G-A is described in ClinVar as [Benign]. Clinvar id is 778204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00338 (515/152192) while in subpopulation EAS AF= 0.0307 (158/5150). AF 95% confidence interval is 0.0268. There are 12 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.605G>A	p.Gly202Asp	missense_variant	2/6	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.605G>A	p.Gly202Asp	missense_variant	2/6		NP_001035943.1
AJAP1	XM_011541786.3	c.605G>A	p.Gly202Asp	missense_variant	2/7		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.605G>A	p.Gly202Asp	missense_variant	2/6	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.605G>A	p.Gly202Asp	missense_variant	2/6	5		ENSP00000367432.3

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152074 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00701 AC: 1695 AN: 241764 Hom.: 28 AF XY: 0.00570 AC XY: 750 AN XY: 131580

Gnomad AFR exome AF: 0.000383

Gnomad AMR exome AF: 0.0338

Gnomad ASJ exome AF: 0.000814

Gnomad EAS exome AF: 0.0255

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.00680

GnomAD4 exome AF: 0.00225 AC: 3281 AN: 1459450 Hom.: 73 Cov.: 37 AF XY: 0.00207 AC XY: 1506 AN XY: 725956

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.000806

Gnomad4 EAS exome AF: 0.0355

Gnomad4 SAS exome AF: 0.00146

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152192 Hom.: 12 Cov.: 33 AF XY: 0.00359 AC XY: 267 AN XY: 74388

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00101 Hom.: 2

Bravo AF: 0.00515

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00590 AC: 716

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.67	.;T
MetaRNN	Benign	0.0067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.24
Sift	Benign	0.052	T;T
Sift4G	Benign	0.60	T;T
Polyphen		1.0	D;D
Vest4		0.22
MVP		0.59
MPC		1.4
ClinPred		0.034	T
GERP RS		5.2
Varity_R		0.33
gMVP		0.32

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: rs76065876; hg19: chr1-4772535; COSMIC: COSV65450190; COSMIC: COSV65450190;