14-22971195-G-A

Position:

• chr14-22971195-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032876.6(AJUBA):​c.*2248C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,460 control chromosomes in the GnomAD database, including 4,063 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 0.23 (4063 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: AJUBA NM_032876.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

Genes affected

AJUBA (HGNC:20250): (ajuba LIM protein) Enables alpha-catenin binding activity and transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; positive regulation of gene silencing by miRNA; and regulation of cellular response to hypoxia. Acts upstream of or within gene silencing by miRNA and positive regulation of protein-containing complex assembly. Located in several cellular components, including Golgi apparatus; P-body; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AJUBA	NM_032876.6	c.*2248C>T		3_prime_UTR_variant	8/8	ENST00000262713.7
AJUBA	NM_198086.3	c.*2248C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AJUBA	ENST00000262713.7	c.*2248C>T		3_prime_UTR_variant	8/8	1	NM_032876.6	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34337 AN: 151348 Hom.: 4059 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.228

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.227 AC: 34367 AN: 151460 Hom.: 4063 Cov.: 31 AF XY: 0.225 AC XY: 16648 AN XY: 73972

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0465

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.234

Alfa AF: 0.228 Hom.: 6827

Bravo AF: 0.223

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.33

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: rs2180834; hg19: chr14-23440404;