1-4711974-C-T

Position:

chr1-4711974-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018836.4(AJAP1):c.104C>T(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,588,056 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00076 ( 10 hom. )

Consequence

AJAP1
NM_018836.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.27

Variant links:

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]

AJAP1 links:

AJAP1 (HGNC:):

AJAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004235029).

BP6

Variant 1-4711974-C-T is Benign according to our data. Variant chr1-4711974-C-T is described in ClinVar as [Benign]. Clinvar id is 787731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000763 (1096/1435792) while in subpopulation AFR AF= 0.0162 (495/30496). AF 95% confidence interval is 0.0151. There are 10 homozygotes in gnomad4_exome. There are 534 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJAP1	NM_018836.4 linkuse as main transcript	c.104C>T	p.Ala35Val	missense_variant	2/6	ENST00000378191.5	NP_061324.1	Q9UKB5
AJAP1	NM_001042478.2 linkuse as main transcript	c.104C>T	p.Ala35Val	missense_variant	2/6		NP_001035943.1	Q9UKB5
AJAP1	XM_011541786.3 linkuse as main transcript	c.104C>T	p.Ala35Val	missense_variant	2/7		XP_011540088.1	Q9UKB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AJAP1	ENST00000378191.5 linkuse as main transcript	c.104C>T	p.Ala35Val	missense_variant	2/6	1	NM_018836.4	ENSP00000367433.3	Q9UKB5
AJAP1	ENST00000378190.7 linkuse as main transcript	c.104C>T	p.Ala35Val	missense_variant	2/6	5		ENSP00000367432.3	Q9UKB5
AJAP1	ENST00000466761.1 linkuse as main transcript	n.107C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.00420

AC:

639

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00131

AC:

284

AN:

216982

Hom.:

AF XY:

0.00106

AC XY:

127

AN XY:

119580

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.000847

Gnomad ASJ exome

AF:

0.00113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000597

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000515

Gnomad OTH exome

AF:

0.000574

GnomAD4 exome

AF:

0.000763

AC:

1096

AN:

1435792

Hom.:

Cov.:

AF XY:

0.000748

AC XY:

534

AN XY:

713910

show subpopulations

Gnomad4 AFR exome

AF:

0.0162

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000994

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.000448

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00421

AC:

641

AN:

152264

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00474

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.00168

AC:

204

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

.;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.094

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

D;D

Vest4

0.22

MVP

0.42

MPC

1.1

ClinPred

0.032

GERP RS

5.1

Varity_R

0.20

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over