rs12351693

Positions:

• chr9-108949235-A-G

Variant summary

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

The NM_003798.4(CTNNAL1):​c.1836-1001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,172 control chromosomes in the GnomAD database, including 486 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 0.073 (486 hom., cov: 32)
• Consequence: CTNNAL1 NM_003798.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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]

ABITRAM (HGNC:1364): (actin binding transcription modulator) Predicted to enable actin filament binding activity and actin monomer binding activity. Predicted to be involved in dendrite morphogenesis; regulation of actin filament polymerization; and regulation of filopodium assembly. Predicted to be located in growth cone. Predicted to be active in several cellular components, including dendrite; filopodium tip; and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

CTNNAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNAL1	NM_003798.4	c.1836-1001T>C		intron_variant		ENST00000325551.9	NP_003789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNAL1	ENST00000325551.9	c.1836-1001T>C		intron_variant		1	NM_003798.4	ENSP00000320434.4
CTNNAL1	ENST00000374595.8	c.1836-1001T>C		intron_variant		1		ENSP00000363723.4
CTNNAL1	ENST00000374594.1	c.39-1001T>C		intron_variant		3		ENSP00000363722.1
ABITRAM	ENST00000374624.7	c.262-1272A>G		intron_variant		3		ENSP00000363754.3

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11099 AN: 152054 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0756

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

GnomAD4 genome AF: 0.0730 AC: 11115 AN: 152172 Hom.: 486 Cov.: 32 AF XY: 0.0770 AC XY: 5728 AN XY: 74378

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0784 Hom.: 119

Bravo AF: 0.0747

Asia WGS AF: 0.108 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.37

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: rs12351693; hg19: chr9-111711515;