9-109003457-C-T

Variant names:

• chr9-109003457-C-T
• rs12555920
• NM_003798.4:c.142-4201G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003798.4(CTNNAL1):​c.142-4201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,118 control chromosomes in the GnomAD database, including 1,478 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 0.13 (1478 hom., cov: 32)
• Consequence: CTNNAL1 NM_003798.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 13 publications found

Genes affected

CTNNAL1 (HGNC:2512): (catenin alpha like 1) Predicted to enable actin filament binding activity and cadherin binding activity. Acts upstream of or within Rho protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376216 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNAL1	NM_003798.4	c.142-4201G>A		intron_variant	Intron 1 of 18	ENST00000325551.9	NP_003789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNAL1	ENST00000325551.9	c.142-4201G>A		intron_variant	Intron 1 of 18	1	NM_003798.4	ENSP00000320434.4
CTNNAL1	ENST00000374595.8	c.142-4201G>A		intron_variant	Intron 1 of 18	1		ENSP00000363723.4
CTNNAL1	ENST00000374593.4	c.142-4201G>A		intron_variant	Intron 1 of 3	3		ENSP00000363721.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19034 AN: 152000 Hom.: 1473 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19067 AN: 152118 Hom.: 1478 Cov.: 32 AF XY: 0.127 AC XY: 9443 AN XY: 74352

African (AFR) AF: 0.214 AC: 8891 AN: 41458

American (AMR) AF: 0.148 AC: 2261 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3470

East Asian (EAS) AF: 0.146 AC: 758 AN: 5176

South Asian (SAS) AF: 0.0709 AC: 342 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1318 AN: 10580

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5114 AN: 68016

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0839 Hom.: 1299

Bravo AF: 0.136

Asia WGS AF: 0.116 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

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: rs12555920; hg19: chr9-111765737;