5-138753726-G-A

Variant names:

• chr5-138753726-G-A
• rs546999400
• NM_001903.5:c.-3+216G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001903.5(CTNNA1):​c.-3+216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 317,062 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: CTNNA1 NM_001903.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.330
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-138753726-G-A is Benign according to our data. Variant chr5-138753726-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1678/152076) while in subpopulation AFR AF = 0.0384 (1595/41514). AF 95% confidence interval is 0.0369. There are 27 homozygotes in GnomAd4. There are 795 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1678 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.-3+216G>A		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+216G>A		intron_variant	Intron 1 of 17	1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1668 AN: 151966 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00125 AC: 207 AN: 164986 Hom.: 3 Cov.: 0 AF XY: 0.00108 AC XY: 91 AN XY: 84344

African (AFR) AF: 0.0347 AC: 148 AN: 4264

American (AMR) AF: 0.00192 AC: 9 AN: 4688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5774

East Asian (EAS) AF: 0.00 AC: 0 AN: 15538

South Asian (SAS) AF: 0.00 AC: 0 AN: 1522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15956

Middle Eastern (MID) AF: 0.00228 AC: 2 AN: 876

European-Non Finnish (NFE) AF: 0.0000851 AC: 9 AN: 105776

Other (OTH) AF: 0.00368 AC: 39 AN: 10592

GnomAD4 genome AF: 0.0110 AC: 1678 AN: 152076 Hom.: 27 Cov.: 32 AF XY: 0.0107 AC XY: 795 AN XY: 74346

African (AFR) AF: 0.0384 AC: 1595 AN: 41514

American (AMR) AF: 0.00379 AC: 58 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67950

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00902 Hom.: 2

Bravo AF: 0.0121

Asia WGS AF: 0.00145 AC: 5 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.7
DANN	Benign	0.92
PhyloP100		-0.33
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs546999400; hg19: chr5-138089415;