chr1-4711974-C-T

Variant names:

• chr1-4711974-C-T
• rs149284997
• NM_018836.4:c.104C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 12/21 in silico tools predict 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.27
• Publications: 7 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 -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 534 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJAP1	NM_018836.4	MANE Select	c.104C>T	p.Ala35Val	missense	Exon 2 of 6	NP_061324.1	Q9UKB5
	AJAP1	NM_001042478.2		c.104C>T	p.Ala35Val	missense	Exon 2 of 6	NP_001035943.1	Q9UKB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJAP1	ENST00000378191.5	TSL:1 MANE Select	c.104C>T	p.Ala35Val	missense	Exon 2 of 6	ENSP00000367433.3	Q9UKB5
	AJAP1	ENST00000378190.7	TSL:5	c.104C>T	p.Ala35Val	missense	Exon 2 of 6	ENSP00000367432.3	Q9UKB5
	AJAP1	ENST00000880749.1		c.104C>T	p.Ala35Val	missense	Exon 2 of 5	ENSP00000550808.1

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 639 AN: 152148 Hom.: 1 Cov.: 34

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

GnomAD2 exomes AF: 0.00131 AC: 284 AN: 216982 AF XY: 0.00106

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 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.: 10 Cov.: 30 AF XY: 0.000748 AC XY: 534 AN XY: 713910

African (AFR) AF: 0.0162 AC: 495 AN: 30496

American (AMR) AF: 0.00112 AC: 45 AN: 40264

Ashkenazi Jewish (ASJ) AF: 0.000994 AC: 25 AN: 25158

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36850

South Asian (SAS) AF: 0.000448 AC: 37 AN: 82546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51730

Middle Eastern (MID) AF: 0.00649 AC: 37 AN: 5700

European-Non Finnish (NFE) AF: 0.000285 AC: 315 AN: 1103664

Other (OTH) AF: 0.00237 AC: 141 AN: 59384

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152264 Hom.: 1 Cov.: 34 AF XY: 0.00395 AC XY: 294 AN XY: 74442

African (AFR) AF: 0.0131 AC: 546 AN: 41562

American (AMR) AF: 0.00261 AC: 40 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68002

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00264 Hom.: 4

Bravo AF: 0.00474

ESP6500AA AF: 0.0118 AC: 52

ESP6500EA AF: 0.000815 AC: 7

ExAC AF: 0.00168 AC: 204

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.094
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.22
MVP		0.42
MPC		1.1
ClinPred		0.032	T
GERP RS		5.1
Varity_R		0.20
gMVP		0.51
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs149284997; hg19: chr1-4772034; COSMIC: COSV65450854;