5-138753541-G-C

Variant names:

• chr5-138753541-G-C
• rs529217936
• NM_001903.5:c.-3+31G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001903.5(CTNNA1):​c.-3+31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 375,156 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0051 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (13 hom.)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0110
• Publications: 0 publications found

Genes affected

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

CTNNA1-AS1 (HGNC:55535): (CTNNA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-138753541-G-C is Benign according to our data. Variant chr5-138753541-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 223743.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00511 (773/151362) while in subpopulation AMR AF = 0.0295 (449/15224). AF 95% confidence interval is 0.0272. There are 14 homozygotes in GnomAd4. There are 385 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 773 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-3+31G>C		intron_variant	Intron 1 of 17	ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.-3+31G>C		intron_variant	Intron 1 of 17	1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.00511 AC: 773 AN: 151254 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000946

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00326

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00346

Gnomad OTH AF: 0.00433

GnomAD4 exome AF: 0.00464 AC: 1039 AN: 223794 Hom.: 13 Cov.: 0 AF XY: 0.00448 AC XY: 511 AN XY: 114088

African (AFR) AF: 0.00164 AC: 10 AN: 6102

American (AMR) AF: 0.0478 AC: 317 AN: 6626

Ashkenazi Jewish (ASJ) AF: 0.000126 AC: 1 AN: 7960

East Asian (EAS) AF: 0.00 AC: 0 AN: 21174

South Asian (SAS) AF: 0.00139 AC: 4 AN: 2882

European-Finnish (FIN) AF: 0.00493 AC: 100 AN: 20266

Middle Eastern (MID) AF: 0.00173 AC: 2 AN: 1154

European-Non Finnish (NFE) AF: 0.00377 AC: 539 AN: 143138

Other (OTH) AF: 0.00455 AC: 66 AN: 14492

GnomAD4 genome AF: 0.00511 AC: 773 AN: 151362 Hom.: 14 Cov.: 32 AF XY: 0.00520 AC XY: 385 AN XY: 73990

African (AFR) AF: 0.000943 AC: 39 AN: 41340

American (AMR) AF: 0.0295 AC: 449 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4812

European-Finnish (FIN) AF: 0.00326 AC: 34 AN: 10430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00346 AC: 234 AN: 67698

Other (OTH) AF: 0.00428 AC: 9 AN: 2102

Alfa AF: 0.00635 Hom.: 2

Bravo AF: 0.00855

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Dec 01, 2015

University of Washington Department of Laboratory Medicine, University of Washington

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.75
PhyloP100		0.011
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs529217936; hg19: chr5-138089230;